表皮生长因子对烟雾吸入性损伤大鼠的治疗作用
|
摘要
目的:以烟雾吸入性损伤大鼠为研究对象,在气道中滴入表皮生长因子(epidermal growth factor,EGF),观察不同剂量EGF对大鼠的治疗作用,以确定EGF的用药剂量,并为EGF临床用药方案(药物剂量、用法)的制定提供参考。
方法:研究分为两部分:1.制作大鼠烟雾吸入性损伤模型:将大鼠随机分为7组——正常对照组,吸入性损伤后1h、6h、12h、24h、48h、72h活杀组,每组6只,在特制装置中烟雾致伤。从大鼠的血气分析,肺系数,大体及病理观察,支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中细胞总数(totalcell count,TC)、巨噬细胞(macrophage,MAC)、中性粒细胞(neutrophil,NEU)、淋巴细胞(lymphocyte,LYM)、红细胞(red blood cell,RBC)、上皮细胞(epithelialcell,EP)分类计数和蛋白浓度等指标多方面评价该模型的致伤效果。2.观察不同剂量EGF对大鼠的治疗效果:将大鼠随机分为4组——对照组、低剂量组(100ug/kg)、中剂量组(150ug/kg)和高剂量组(200ug/kg),气管内分别滴入生理盐水(normal sodium,NS)和不同浓度EGF(50ug/ml、75ug/ml、100ug/ml)2ml/kg,12h后腹腔注射BrdU(100mg/kg),观察吸入性损伤大鼠致伤后72h的血气分析,肺系数(pulmonary index,PI),大体及病理观察,支气管肺泡灌洗液中细胞总数、巨噬细胞、中性粒细胞、淋巴细胞、红细胞、上皮细胞分类计数和蛋白浓度等指标,观察EGF的治疗作用;并进行BrdU免疫组化染色,观察EGF对气道上皮细胞的增殖作用。
结果:1.本研究制作的大鼠烟雾吸入性损伤的模型致伤情况达到预期结果,多次重复,效果稳定。血气分析显示:PH呈下降趋势,致伤后12h、24h、48h、72h与对照组相比差异非常显著,且24h最为低;PaO_2明显降低,伤后1h与对照组相比即有显著差异直至观察结束;PaCO_2呈上升趋势,致伤后24h、48h、72h与对照组相比差异显著;12h、24h、48h、72h肺系数显著升高,于伤后24h最为明显,之后逐渐降低;支气管肺泡灌洗液中:细胞总数于12h后明显增加;巨噬细胞、红细胞于24h后明显增加:中性粒细胞、淋巴细胞于6h后明显增加;上皮细胞于48h时明显增加;对照组大鼠BALF中蛋白浓度为(11.303±5.634)ug/ml,致伤组呈上升趋势,48h为[46.956±15.175,P＜0.05)],72h时为[(60.781±35.354,P＜0.01)]。
2.致伤后气管内滴入生理盐水和不同剂量EGF,结果显示:PH随剂量增加呈上升趋势,与对照组相比中、高剂量组差异显著;PaO_2呈上升趋势,PaCO_2呈下降趋势,与对照组相比中、高剂量组差异显著,其中高剂量组PaO_2差异非常显著。高剂量组与低剂量组相比,PaO_2也有明显上升;肺系数和BALF中蛋白浓度随EGF剂量的增加呈下降趋势,但低剂量组差异并不显著,中、高剂量组肺系数和蛋白浓度则下降明显;支气管肺泡灌洗液中:三个治疗组与对照组相比细胞总数、巨噬细胞、中性粒细胞、淋巴细胞均明显降低;红细胞、上皮细胞在中、高剂量组中明显降低,低剂量组则下降不明显;增殖上皮细胞的标记指数:治疗组肺上皮细胞标记指数(label index,LI)呈上升趋势,其中高剂量组与对照组和低剂量组相比差异非常显著。
结论:烟雾吸入性损伤可以导致肺水肿、气道炎性浸润和上皮细胞破坏;外源性EGF可清除肺水肿,抑制气道炎症,促进损伤上皮的增殖和修复,恢复上皮形态和功能的完整性,且随着剂量的增加效果更为明显。
Objective: Through observing the therapeutical effect on smoke inhalation injury on rats with different doses of epidermal growth factor, which are infused in their airways, the doses and the method of epidermal growth factor can be determined and the reference for clinical treatment programmes (dosage, usage) can be provided.
Methods: The study was divided into two parts: 1. Rat model of smoke inhalation injury: rats were randomly divided into 7 groups——control group and six experiment groups in which rats were killed in 1h, 6h, 12h, 24h, 48h, 72h after inhalation injury. Rats were vulnerated in a special device smoke injuries. To evaluate the effect of smoke inhalation injury model through multiple factors: blood gas analysis, lung index, gross morphometric and pathological obserevation, the count of total number of cells, macrophages, neutrophils, lymphocytes, red blood cells, epithelial cells and protein concentration in bronchoalveolar lavage fluid.
2. To observe therapeutic efficacy of different doses of epidermal growth factor on rats: Rats were randomly divided into four groups——control group, low dose group(100ug/kg), medium dose group (150ug/kg) and high dose group (200ug/kg), normal sodium and different concentrations of epidermal growth factor(50ug/ml, 75ug/ml, 100ug/ml) 2ml/kg were dropped into airways of rats respectively, BrdU (100mg/kg) was intraperitoneal injected after 12 hours. Rats were killed after 72h and therapeutic efficacy was evaluated through multiple factors: blood gas analysis, lung index, gross morphometric and pathological obserevation , the count of total number of cells, macrophages, neutrophils, lymphocytes, red blood cells, epithelial cells and protein concentration in bronchoalveolar lavage fluid. And we estimated epidermal growth factor on airway epithelial cell proliferation through observing immunohistochemical staining of BrdU.
Results: 1 .This model of smoke inhalation injury on rats achieves the desire. Blood gas analysis showed that: PH was on a downward trend, and there was significant difference between the groups of 12h, 24h, 48h, 72h after injury and the control group, and PH was the lowest 24h after inhalation injury. PaO_2 decreased significantly while there was significant difference between the groups of 1h,6h,12h, 24h, 48h, 72h after injury and the control group. PaCO_2 was on a upward trend, and there was significant difference between the groups of 24h, 48h, 72h after injury and the control group. There was significant difference between the groups of 12h, 24h, 48h, 72h after injury and the control group in lung index. Lung index reached the peak in 24h after injury, then reduced gradually. Bronchoalveolar lavage fluid: Total number of cells greatly increased after 12h. Macrophage cells, red blood cells significantly increased after 24h.Neutrophils, lymphocytes significantly increased after 6h.Epithelial cells significantly increased at 48h. Protein concentrations in bronchoalveolar lavage fluid of control group was (11.303±5.634)ug/ml, it was on upward trend after injury, [46.956±15.175, P <0.05)] at 48h, [(60.781±35.354, P <0.01)] at 72h, respectively. 2. Saline and different doses of epidermal growth factor were dropped into the airway of rats after injury, and the results demonstrated: PH was on a upward trend with the dose increasing, and there was significant difference between medium dose group, high dose group and control group. PaO_2 was on the upward trend, and PaCO_2 was on a downward trend. There was significant difference between medium dose group, high dose group and control group. PaO_2 of high dose group increased obviously compared with that of low dose group. Lung index and protein concentrations in bronchoalveolar lavage fluid were on downward trend with the doses of epidermal growth factor increased. There was a significant difference between medium dose group, high dose group and control group, but low dose group had no significant differences. Bronchoalveolar lavage fluid: the total number of cells, macrophages, neutrophils, lymphocytes of three treatment groups significantly decreased compared with the control group. Red blood cells and epithelial cells of medium dose group and high dose group significantly decreased compared with the control group. Labeling index of three treatment groups was on the upward trend, high dose group significantly increased compared with the control group and low dose group.
Conclusion: smoke inhalation injury can lead to pulmonary edema, airway inflammatory infiltration and cell damage. Exogenous epidermal growth factor can remove pulmonary edema, inhibit airway inflammation, promote the proliferation and repair of epithelial injury, and restore the form and function of epithelial integrity. With the increase of doses ,the effects are more obvious.
方法:研究分为两部分:1.制作大鼠烟雾吸入性损伤模型:将大鼠随机分为7组——正常对照组,吸入性损伤后1h、6h、12h、24h、48h、72h活杀组,每组6只,在特制装置中烟雾致伤。从大鼠的血气分析,肺系数,大体及病理观察,支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中细胞总数(totalcell count,TC)、巨噬细胞(macrophage,MAC)、中性粒细胞(neutrophil,NEU)、淋巴细胞(lymphocyte,LYM)、红细胞(red blood cell,RBC)、上皮细胞(epithelialcell,EP)分类计数和蛋白浓度等指标多方面评价该模型的致伤效果。2.观察不同剂量EGF对大鼠的治疗效果:将大鼠随机分为4组——对照组、低剂量组(100ug/kg)、中剂量组(150ug/kg)和高剂量组(200ug/kg),气管内分别滴入生理盐水(normal sodium,NS)和不同浓度EGF(50ug/ml、75ug/ml、100ug/ml)2ml/kg,12h后腹腔注射BrdU(100mg/kg),观察吸入性损伤大鼠致伤后72h的血气分析,肺系数(pulmonary index,PI),大体及病理观察,支气管肺泡灌洗液中细胞总数、巨噬细胞、中性粒细胞、淋巴细胞、红细胞、上皮细胞分类计数和蛋白浓度等指标,观察EGF的治疗作用;并进行BrdU免疫组化染色,观察EGF对气道上皮细胞的增殖作用。
结果:1.本研究制作的大鼠烟雾吸入性损伤的模型致伤情况达到预期结果,多次重复,效果稳定。血气分析显示:PH呈下降趋势,致伤后12h、24h、48h、72h与对照组相比差异非常显著,且24h最为低;PaO_2明显降低,伤后1h与对照组相比即有显著差异直至观察结束;PaCO_2呈上升趋势,致伤后24h、48h、72h与对照组相比差异显著;12h、24h、48h、72h肺系数显著升高,于伤后24h最为明显,之后逐渐降低;支气管肺泡灌洗液中:细胞总数于12h后明显增加;巨噬细胞、红细胞于24h后明显增加:中性粒细胞、淋巴细胞于6h后明显增加;上皮细胞于48h时明显增加;对照组大鼠BALF中蛋白浓度为(11.303±5.634)ug/ml,致伤组呈上升趋势,48h为[46.956±15.175,P＜0.05)],72h时为[(60.781±35.354,P＜0.01)]。
2.致伤后气管内滴入生理盐水和不同剂量EGF,结果显示:PH随剂量增加呈上升趋势,与对照组相比中、高剂量组差异显著;PaO_2呈上升趋势,PaCO_2呈下降趋势,与对照组相比中、高剂量组差异显著,其中高剂量组PaO_2差异非常显著。高剂量组与低剂量组相比,PaO_2也有明显上升;肺系数和BALF中蛋白浓度随EGF剂量的增加呈下降趋势,但低剂量组差异并不显著,中、高剂量组肺系数和蛋白浓度则下降明显;支气管肺泡灌洗液中:三个治疗组与对照组相比细胞总数、巨噬细胞、中性粒细胞、淋巴细胞均明显降低;红细胞、上皮细胞在中、高剂量组中明显降低,低剂量组则下降不明显;增殖上皮细胞的标记指数:治疗组肺上皮细胞标记指数(label index,LI)呈上升趋势,其中高剂量组与对照组和低剂量组相比差异非常显著。
结论:烟雾吸入性损伤可以导致肺水肿、气道炎性浸润和上皮细胞破坏;外源性EGF可清除肺水肿,抑制气道炎症,促进损伤上皮的增殖和修复,恢复上皮形态和功能的完整性,且随着剂量的增加效果更为明显。
Objective: Through observing the therapeutical effect on smoke inhalation injury on rats with different doses of epidermal growth factor, which are infused in their airways, the doses and the method of epidermal growth factor can be determined and the reference for clinical treatment programmes (dosage, usage) can be provided.
Methods: The study was divided into two parts: 1. Rat model of smoke inhalation injury: rats were randomly divided into 7 groups——control group and six experiment groups in which rats were killed in 1h, 6h, 12h, 24h, 48h, 72h after inhalation injury. Rats were vulnerated in a special device smoke injuries. To evaluate the effect of smoke inhalation injury model through multiple factors: blood gas analysis, lung index, gross morphometric and pathological obserevation, the count of total number of cells, macrophages, neutrophils, lymphocytes, red blood cells, epithelial cells and protein concentration in bronchoalveolar lavage fluid.
2. To observe therapeutic efficacy of different doses of epidermal growth factor on rats: Rats were randomly divided into four groups——control group, low dose group(100ug/kg), medium dose group (150ug/kg) and high dose group (200ug/kg), normal sodium and different concentrations of epidermal growth factor(50ug/ml, 75ug/ml, 100ug/ml) 2ml/kg were dropped into airways of rats respectively, BrdU (100mg/kg) was intraperitoneal injected after 12 hours. Rats were killed after 72h and therapeutic efficacy was evaluated through multiple factors: blood gas analysis, lung index, gross morphometric and pathological obserevation , the count of total number of cells, macrophages, neutrophils, lymphocytes, red blood cells, epithelial cells and protein concentration in bronchoalveolar lavage fluid. And we estimated epidermal growth factor on airway epithelial cell proliferation through observing immunohistochemical staining of BrdU.
Results: 1 .This model of smoke inhalation injury on rats achieves the desire. Blood gas analysis showed that: PH was on a downward trend, and there was significant difference between the groups of 12h, 24h, 48h, 72h after injury and the control group, and PH was the lowest 24h after inhalation injury. PaO_2 decreased significantly while there was significant difference between the groups of 1h,6h,12h, 24h, 48h, 72h after injury and the control group. PaCO_2 was on a upward trend, and there was significant difference between the groups of 24h, 48h, 72h after injury and the control group. There was significant difference between the groups of 12h, 24h, 48h, 72h after injury and the control group in lung index. Lung index reached the peak in 24h after injury, then reduced gradually. Bronchoalveolar lavage fluid: Total number of cells greatly increased after 12h. Macrophage cells, red blood cells significantly increased after 24h.Neutrophils, lymphocytes significantly increased after 6h.Epithelial cells significantly increased at 48h. Protein concentrations in bronchoalveolar lavage fluid of control group was (11.303±5.634)ug/ml, it was on upward trend after injury, [46.956±15.175, P <0.05)] at 48h, [(60.781±35.354, P <0.01)] at 72h, respectively. 2. Saline and different doses of epidermal growth factor were dropped into the airway of rats after injury, and the results demonstrated: PH was on a upward trend with the dose increasing, and there was significant difference between medium dose group, high dose group and control group. PaO_2 was on the upward trend, and PaCO_2 was on a downward trend. There was significant difference between medium dose group, high dose group and control group. PaO_2 of high dose group increased obviously compared with that of low dose group. Lung index and protein concentrations in bronchoalveolar lavage fluid were on downward trend with the doses of epidermal growth factor increased. There was a significant difference between medium dose group, high dose group and control group, but low dose group had no significant differences. Bronchoalveolar lavage fluid: the total number of cells, macrophages, neutrophils, lymphocytes of three treatment groups significantly decreased compared with the control group. Red blood cells and epithelial cells of medium dose group and high dose group significantly decreased compared with the control group. Labeling index of three treatment groups was on the upward trend, high dose group significantly increased compared with the control group and low dose group.
Conclusion: smoke inhalation injury can lead to pulmonary edema, airway inflammatory infiltration and cell damage. Exogenous epidermal growth factor can remove pulmonary edema, inhibit airway inflammation, promote the proliferation and repair of epithelial injury, and restore the form and function of epithelial integrity. With the increase of doses ,the effects are more obvious.
引文
[1]. Sakano T, Okerberg CV, Shippee RL, Sanchez J, Mason AD, Jr., Pruitt BA, Jr.A rabbit model of inhalation injury. The Journal of trauma. 1993 Mar;34(3):411-6.
[2]. Shun-Zhen Q, Hong-Hang Z. The effects of inhaled nitric oxide on the levels of cGMP plasma and lung tissue in a canine model of smoke inhalation injury. Burns.2002 Jun;28(4):299-304.
[3]. Cox RA, Burke AS, Soejima K, Murakami K, Katahira J, Traber LD, et al.Airway obstruction in sheep with burn and smoke inhalation injuries. American journal of respiratory cell and molecular biology. 2003 Sep;29(3 Pt 1):295-302.
[4]. Westphal M, Morita N, Enkhbaatar P, Murakami K, Traber L, Traber DL.Acute effects of combined burn and smoke inhalation injury on carboxyhemoglobin formation, tissue oxygenation, and cardiac performance. Biochem Biophys Res Commun. 2004 May 7;317(3):945-9.
[5]. Pryor WA. Biological effects of cigarette smoke, wood smoke, and the smoke from plastics: the use of electron spin resonance. Free radical biology and medicine.1992 Dec;13(6):659-76.
[6]. Demling R, Ikegami K, Lalonde C. Increased lipid peroxidation and decreased antioxidant activity correspond with death after smoke exposure in the rat. The Journal of burn care and rehabilitation. 1995 Mar-Apr;16(2 Pt 1):104-10.
[7]. Demling R, Lalonde C, Picard L, Blanchard J. Changes in lung and systemic oxidant and antioxidant activity after smoke inhalation. Shock (Augusta, Ga. 1994 Feb;1(2):101-7.
[8]. Haponik EF. Clinical smoke inhalation injury: pulmonary effects. Occupational medicine (Philadelphia, Pa. 1993 Jul-Sep;8(3):430-68.
[9]. Quinn DA, Robinson D, Jung W, Hales CA. Role of sulfidopeptide leukotrienes in synthetic smoke inhalation injury in sheep. J Appl Physiol. 1990 May;68(5):1962-9.
[10]. Chung KF, Rogers DF, Barnes PJ, Evans TW. The role of increased airway microvascular permeability and plasma exudation in asthma. Eur Respir J. 1990 Mar;3(3):329-37.
[11]. Barnes PJ, Chung KF, Page CP. Inflammatory mediators of asthma: an update. Pharmacological reviews. 1998 Dec;50(4):515-96.
[12]. Soejima K, McGuire R, Snyder Nt, Uchida T, Szabo C, Salzman A, et al. The effect of inducible nitric oxide synthase (iNOS) inhibition on smoke inhalation injury in sheep. Shock (Augusta, Ga. 2000;13(4):261-6.
[13]. Murakami K, Traber DL. Pathophysiological basis of smoke inhalation injury.News Physiol Sci. 2003 Jun;18:125-9.
[14]. Enkhbaatar P, Kikuchi Y, Traber LD, Westphal M, Morita N, Maybauer MO,et al. Effect of inhaled nitric oxide on pulmonary vascular hyperpermeability in sheep following smoke inhalation. Burns. 2005 Dec;31(8):1013-9.
[15]. Abdi S, Herndon DN, Traber LD, Ashley KD, Stothert JC, Jr., Maguire J, et al. Lung edema formation following inhalation injury: role of the bronchial blood flow. J Appl Physiol. 1991 Aug;71(2):727-34.
16. Isago T, Noshima S, Traber LD, Herndon DN, Traber DL. Analysis of pulmonary microvascular permeability after smoke inhalation. J Appl Physiol. 1991 Oct;71(4):1403-8.
[17]. Basadre JO, Sugi K, Traber DL, Traber LD, Niehaus GD, Herndon DN. The effect of leukocyte depletion on smoke inhalation injury in sheep. Surgery. 1988 Aug;104(2):208-15.
[18]. Ahn SY, Sugi K, Talke P, Theissen JL, Linares HA, Traber LD, et al. Effects of allopurinol on smoke inhalation in the ovine model. J Appl Physiol. 1990 Jan;68(1):228-34.
[19]. Ambiavagar M, Chalon J, Zargham I. Tracheobronchial cytologic changes following lower airway thermal injury. A preliminary report. J Trauma. 1974 Apr,14(4):280-9.
[20]. Traber DL, Linares HA, Herndon DN, Prien T. The pathophysiology of inhalation injury~a review. Burns Incl Therm Inj. 1988 Oct;14(5):357-64.
[21]. Leal Filho MB, Morandin RC, de Almeida AR, Cambiucci EC, Metze K,Borges G, et al. Hemodynamic parameters and neurogenic pulmonary edema following spinal cord injury: an experimental model. Arquivos de neuro-psiquiatria.2005 Dec;63(4):990-6.
[22].Traber DL,Hemdon DN,Stein MD,Traber LD,Flynn JT,Niehaus GD.The pulmonary lesion of smoke inhalation in an ovine model.Circulatory shock.1986;18(4):311-23.
[23].Hubbard GB,Langlinais PC,Shimazu T,Okerberg CV,Mason AD,Jr.,Pruitt BA,Jr.The morphology of smoke inhalation injury in sheep.J Trauma.1991Nov;31(11):1477-86.
[24].Hemdon DN,Langner F,Thompson P,Linares HA,Stein M,Traber DL.Pulmonary injury in burned patients.The Surgical clinics of North America.1987Feb;67(1):31-46.
[25].Takemura R,Werb Z.Secretory products of macrophages and their physiological functions.Am J Physiol.1984 Jan;246(1 Pt 1):C1-9.
[26].Bidani A,Wang CZ,Heming TA.Early effects of smoke inhalation on alveolar macrophage functions.Burns.1996 Mar;22(2):101-6.
[27].Cohen.S.Epidermal growth factor.Nobel lecture.Biosci Rep.1986(6):1017-28.
[28].Sinha A,Nightingale J,West KP,Berlanga-Acosta J,Playford RJ.Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis.N Engl J Med.2003 Jul 24;349(4):350-7.
[29].Wilson SE,Lloyd SA.Epidermal growth factor and its receptor,basic fibroblast growth factor,transforming growth factor beta-1,and interleukin-1 alpha messenger RNA production in human corneal endothelial cells.Invest Ophthalmol Vis Sci.1991 Sep;32(10):2747-56.
[30].Tuomela T,Miettinen P,Pesonen K,Viinikka L,Perheentupa J.Epidermal growth factor in mice:effects of estradiol,testosterone and dexamethasone.Acta endocrinologica.1990 Aug;123(2):211-7.
[31].Kasselberg AG,Orth DN,Gray ME,Stahlman MT.Immunocytochemical localization of human epidermal growth factor/urogastrone in several human tissues.J Histochem Cytochem.1985 Apr;33(4):315-22.
[32].Patel JD.Role of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of bronchoalveolar carcinoma.Clinical lung cancer.2004 Dec;6Suppl 1:S43-7.
[33]. Tesfaigzi J, Johnson NF, Lechner JF. Induction of EGF receptor and erbB-2 during endotoxin-induced alveolar type II cell proliferation in the rat lung. International journal of experimental pathology. 1996 Aug;77(4):143-54.
[34]. Carpenter G, Cohen S. Epidermal growth factor. The Journal of biological chemistry. 1990 May 15;265(14):7709-12.
[35]. Abe K, Saito H. The mitogen-activated protein kinase cascade mediates neurotrophic effect of epidermal growth factor in cultured rat hippocampal neurons.Neurosci Lett. 2000 Mar 17;282(1-2):89-92.
[36]. Huang Y, Chang Y, Wang X, Jiang J, Frank SJ. Growth hormone alters epidermal growth factor receptor binding affinity via activation of extracellular signal-regulated kinases in 3T3-F442A cells. Endocrinology. 2004 Jul;145(7):3297-306.
[37]. Saito T, Okada S, Ohshima K, Yamada E, Sato M, Uehara Y, et al.Differential activation of epidermal growth factor (EGF) receptor downstream signaling pathways by betacellulin and EGF. Endocrinology. 2004 Sep;145(9):4232-43.
[38]. Khan SM, Oliver RH, Yeh J. Epidermal growth factor receptor inhibition by tyrphostin 51 induces apoptosis in luteinized granulosa cells. J Clin Endocrinol Metab.2005 Jan;90(1):469-73.
[39]. Sheng G, Bernabe KQ, Guo J, Warner BW. Epidermal growth factor receptor-mediated proliferation of enterocytes requires p21wafl/cipl expression.Gastroenterology. 2006 Jul;131(1):153-64.
[40]. Horbar JD, Carpenter JH, Buzas J, Soil RF, Suresh G, Bracken MB, et al. Timing of initial surfactant treatment for infants 23 to 29 weeks' gestation: is routine practice evidence based? Pediatrics. 2004 Jun;113(6):1593-602.
[41]. Clegg GR, Tyrrell C, McKechnie SR, Beers MF, Harrison D, McElroy MC.Coexpression of RTI40 with alveolar epithelial type II cell proteins in lungs following injury: identification of alveolar intermediate cell types. Am J Physiol Lung Cell Mol Physiol. 2005 Sep;289(3):L382-90.
[42]. Guazzi M. Alveolar-capillary membrane dysfunction in heart failure:evidence of a pathophysiologic role. Chest. 2003 Sep;124(3):1090-102.
[43]. Tesfaigzi Y. Roles of apoptosis in airway epithelia. Am J Respir Cell Mol Biol. 2006 May;34(5):537-47.
[44]. McDowell EM, Becci PJ, Schurch W, Trump BF. The respiratory epithelium.VII. Epidermoid metaplasia of hamster tracheal epithelium during regeneration following mechanical injury. Journal of the National Cancer Institute. 1979 Apr;62(4):995-1008.
[45]. Fan WH, Lu YL, Deng F, Ge XM, Liu S, Tang PH. EGFR antisense RNA blocks expression of the epidermal growth factor receptor and partially reverse the malignant phenotype of human breast cancer MDA-MB-231 cells. Cell research.1998 Mar;8(1):63-71.
[46]. Kim JS, McKinnis VS, Nawrocki A, White SR. Stimulation of migration and wound repair of guinea-pig airway epithelial cells in response to epidermal growth factor. Am J Respir Cell Mol Biol. 1998 Jan;18(1):66-74.
[47]. Zahm JM, Kaplan H, Herard AL, Doriot F, Pierrot D, Somelette P, et al. Cell migration and proliferation during the in vitro wound repair of the respiratory epithelium. Cell Motil Cytoskeleton. 1997;37(1):33-43.
[48]. Erjefalt JS, Erjefalt I, Sundler F, Persson CG In vivo restitution of airway epithelium. Cell Tissue Res. 1995 Aug;281(2):305-16.
[49]. White SR DD, Rabe KF, et al. Role of very late adhesion integrins in mediating repair of human airway epithelial cell monolayers after mechanical injury.Am J Respir Cell Mol Biol. 1999(20):787-96.
[50]. Jost M, Kari C, Rodeck U. The EGF receptor - an essential regulator of multiple epidermal functions. Eur J Dermatol. 2000 Oct-Nov;10(7):505-10.
[51]. Tyner JW, Kim EY, Ide K, Pelletier MR, Roswit WT, Morton JD, et al.Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13 transdifferentiation signals. J Clin Invest. 2006 Feb;116(2):309-21.
[52]. Raaberg L, Nexo E, Buckley S, Luo W, Snead ML, Warburton D. Epidermal growth factor transcription, translation, and signal transduction by rat type II pneumocytes in culture. Am J Respir Cell Mol Biol. 1992 Jan;6(l):44-9.
[53]. Plopper CG, St George JA, Read LC, Nishio SJ, Weir AJ, Edwards L, et al.Acceleration of alveolar type II cell differentiation in fetal rhesus monkey lung by administration of EGF.Am J Physiol.1992 Mar;262(3 Pt 1):L313-21.
[54].Al-Salmi QA,Walter JN,Colasurdo GN,Sockrider MM,Smith EO,Takahashi H,et al.Serum KL-6 and surfactant proteins A and D in pediatric interstitial lung disease.Chest.2005 Jan;127(1):403-7.
[55].Clark H,Reid K.The potential of recombinant surfactant protein D therapy to reduce inflammation in neonatal chronic lung disease,cystic fibrosis,and emphysema.Arch Dis Child.2003 Nov;88(11):981-4.
[56].Kattwinkel J.Synthetic surfactants:the search goes on.Pediatrics.2005Apr;115(4):1075-6.
[57].Gratzner HG.Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine:A new reagent for detection of DNA replication.Science(New York,NY.1982 Oct 29;218(4571):474-5.
[58].Barrow RE,Wang CZ,Evans MJ,Herndon DN.Growth factors accelerate epithelial repair in sheep trachea.Lung.1993;171(6):335-44.
[59].Garat C,Meignan M,Matthay MA,Luo DF,Jayr C.Alveolar epithelial fluid clearance mechanisms are intact after moderate hyperoxic lung injury in rats.Chest.1997 May;111(5):1381-8.
[60].Montaner JS,Tsang J,Evans KG,Mullen JB,Bums AR,Walker DC,et al.Alveolar epithelial damage.A critical difference between high pressure and oleic acid-induced low pressure pulmonary edema.The Journal of clinical investigation.1986 Jun;77(6):1786-96.
[61].Borok Z,Hami A,Danto SI,Lubman RL,Kim KJ,Crandall ED.Effects of EGF on alveolar epithelial junctional permeability and active sodium transport.Am J Physiol.1996 Apr;270(4 Pt 1):L559-65.
[62].Skou JC.The identification of the sodium pump.Biosci Rep.2004Aug-Oct;24(4-5):436-51.
[63].Blanco G.Mercer RW.Isozymes of the Na-K-ATPase:heterogeneity in structure,diversity in function.Am J Physiol.1998 Nov;275(5 Pt 2):F633-50.
[64].柳琪林,胡森,陆江阳,王谊冰,杨毅,盛志勇.表皮细胞生长因子对吸入性损伤大鼠肺泡Ⅱ型细胞增殖和肺水转运的作用.中国危重病急救医学.2002年12月:14(12):719-22.
[65]. Sznajder JI, Ridge KM, Yeates DB, Ilekis J, Olivera W. Epidermal growth factor increases lung liquid clearance in rat lungs. J Appl Physiol. 1998 Sep;85(3):1004-10.
[66]. Sibille Y, Reynolds HY. Macrophages and polymorphonuclear neutrophils in lung defense and injury. The American review of respiratory disease. 1990 Feb;141(2):471-501.
[67]. Berman JS, Beer DJ, Theodore AC, Kornfeld H, Bernardo J, Center DM.Lymphocyte recruitment to the lung. The American review of respiratory disease.1990 Jul;142(1):238-57.
[68]. Beutler BA, Milsark IW, Cerami A. Cachectin/tumor necrosis factor:production, distribution, and metabolic fate in vivo. J Immunol. 1985 Dec;135(6):3972-7.
[69]. Vassalli P. The pathophysiology of tumor necrosis factors. Annual review of immunology. 1992;10:411-52.
[70]. Zhang K, Gharaee-Kermani M, McGarry B, Remick D, Phan SH.TNF-alpha-mediated lung cytokine networking and eosinophil recruitment in pulmonary fibrosis. J Immunol. 1997 Jan 15;158(2):954-9.
[71]. Imrich A, Ning YY, Koziel H, Coull B, Kobzik L. Lipopolysaccharide priming amplifies lung macrophage tumor necrosis factor production in response to air particles. Toxicology and applied pharmacology. 1999 Sep 1;159(2): 117-24.
[72]. Conroy DM, Francischi JN, Sirois P. Effect of tumor necrosis factor receptor binding protein on cell infiltration induced by lipopolysaccharide and Sephadex beads in guinea pig lung. Inflammation. 1995 Apr;19(2):233-43.
[73]. Whitsett JA, Clark JC, Wispe JR, Pryhuber GS. Effects of TNF-alpha and phorbol ester on human surfactant protein and MnSOD gene transcription in vitro. The American journal of physiology. 1992 Jun;262(6 Pt 1):L688-93.
[74]. Li X, Xing XM, Zhang JS, Tan YR. [Effect of vasoactive intestinal peptide and epidermal growth factor on the adhesion of eosinophils to bronchial epithelial cells]. Zhong nan da xue xue bao Yi xue ban = Journal of Central South University.2006 Oct;31(5):772-5,81.
[75]. Casaco A, Ledon N, Gonzalez A, Merino N, Perez R. Topical anti-inflammatory activity of human recombinant epidermal growth factor.Skin Pharmacol Appl Skin Physiol.1999 Jan-Apr;12(1-2):79-84.
[76].Rocourt DV,Mehta VB,Besner GE.Heparin-binding EGF-like growth factor decreases inflammatory cytokine expression after intestinal ischemia/reperfusion injury.J Surg Res.2007 May 15;139(2):269-73.
[77].Gospodarowicz D,Mescher AL,Birdwell CR.Control of cellular proliferation by the fibroblast and epidermal growth factors.National Cancer Institute monograph.1978 May(48):109-30.
[78].赵永健,刘群.重组人表皮生长因子治疗吸入性损伤的临床观察.中华烧伤杂志.2004年2月:20(1):47.
[79].汪涛.表皮细胞生长因子治疗吸入性损伤的临床观察.中华烧伤杂志.2003年10月;19(5):303.
[80].赵英,廖立新,杨大华,李国辉.表皮细胞生长因子对烧伤合并吸入性损伤的治疗作用.第二军医大学学报.2005年9月;26(9):1066-7.
[1].Cohen S.Nobel lecture.Epidermal growth factor.Biosci Rep.1986Dec;6(12):1017-28.
[2].Sinha A,Nightingale J,West KP,Berlanga-Acosta J,Playford RJ.Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis.N Engl J Med.2003 Jul 24;349(4):350-7.
[3].G.R.Clegg CT,S.R.McKechnie,M.F.Beers,D.Harrison and M.C.McElroy.Coexpression of RTI40 with alveolar epithelial type Ⅱ cell proteins in lungs following injury:identification of alveolar intermediate cell types.Am J Physiol Lung Cell Mol Physiol,September 1.2005;289(3):L382-L90.
[4].Guazzi M.Alveolar-capillary membrane dysfunction in heart failure:evidence of a pathophysiologic role.Chest.2003 Sep;124(3):1090-102.
[5].Puddicombe SM,Torres-Lozano C,Richter A,Bucchieri F,Lordan JL,Howarth PH,et al.Increased expression of p21(waf)cyclin-dependent kinase inhibitor in asthmatic bronchial epithelium.Am J Respir Cell Mol Biol.2003Jan;28(1):61-8.
[6].Puddicombe SM,Polosa R,Richter A,Krishna MT,Howarth PH,Holgate ST,et al.Involvement of the epidermal growth factor receptor in epithelial repair in asthma.Faseb J.2000 Jul;14(10):1362-74.
[7].Jost M,Kari C,Rodeck U.The EGF receptor-an essential regulator of multiple epidermal functions.Eur J Dermatol.2000 Oct-Nov;10(7):505-10.
[8].Burgel PR,Nadel JA.Roles of epidermal growth factor receptor activation in epithelial cell repair and mucin production in airway epithelium.Thorax.2004Nov;59(11):992-6.
[9].Tyner JW,Kim EY,Ide K,Pelletier MR,Roswit WT,Morton JD,et al.Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13transdifferentiation signals.J Clin Invest.2006 Feb;116(2):309-21.
[10].Wang HQ,Quan T,He T,Franke TF,Voorhees JJ,Fisher GJ.Epidermal growth factor receptor-dependent,NF-kappaB-independent activation of the phosphatidylinositol 3-kinase/Akt pathway inhibits ultraviolet irradiation-induced caspases-3,-8,and -9 in human keratinocytes.J Biol Chem.2003 Nov 14;278(46):45737-45.
[11].Allan LA,Morrice N,Brady S,Magee G,Pathak S,Clarke PR.Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK.Nat Cell Biol.2003Jul;5(7):647-54.
[12].Abe K,Saito H.The mitogen-activated protein kinase cascade mediates neurotrophic effect of epidermal growth factor in cultured rat hippocampal neurons.Neurosci Lett.2000 Mar 17;282(1-2):89-92.
[13].Huang Y,Chang Y,Wang X,Jiang J,Frank SJ.Growth hormone alters epidermal growth factor receptor binding affinity via activation of extracellular signal-regulated kinases in 3T3-F442A cells.Endocrinology.2004Jul;145(7):3297-306.
[14].Saito T,Okada S,Ohshima K,Yamada E,Sato M,Uehara Y,et al.Differential activation of epidermal growth factor(EGF)receptor downstream signaling pathways by betacellulin and EGF.Endocrinology.2004Sep;145(9):4232-43.
[15].Khan SM,Oliver RH,Yeh J.Epidermal growth factor receptor inhibition by tyrphostin 51 induces apoptosis in luteinized granulosa cells.J Clin Endocrinol Metab.2005 Jan;90(1):469-73.
[16].Sheng G,Bernabe KQ,Guo J,Warner BW.Epidermal growth factor receptor-mediated proliferation of enterocytes requires p21waf1/cip1 expression.Gastroenterology.2006 Jul;131(1):153-64.
[17].Functional genomics of lung disease.Second annual Pittsburgh International Lung Conference,October 2003.Am J Respir Cell Mol Biol.2004 Aug;31(2Suppl):S1-81.
[18].Kim JS,McKinnis VS,Nawrocki A,White SR.Stimulation of migration and wound repair of guinea-pig airway epithelial cells in response to epidermal growth factor.Am J Respir Cell Mol Biol.1998 Jan;18(1):66-74.
[19].White SR,Dorscheid DR,Rabe KF,Wojcik KR,Hamann KJ.Role of very late adhesion integrins in mediating repair of human airway epithelial cell monolayers after mechanical injury.Am J Respir Cell Mol Biol.1999 Apr;20(4):787-96.
[20].柳琪林,胡森,陆江阳,王谊冰,杨毅,盛志勇.表皮细胞生长因子对吸入性损伤大鼠肺泡Ⅱ型细胞增殖和肺水转运的作用.中国危重病急救医学.2002年12月:14(12):719-22.
[21].Nielsen HC,Martin A,Volpe MV,Hatzis D,Vosatka RJ.Growth factor control of growth and epithelial differentiation in embryonic lungs.Biochem Mol Med.1997 Feb;60(1):38-48.
[22].Plopper CG,St George JA,Read LC,Nishio SJ,Weir AJ,Edwards L,et al.Acceleration of alveolar type Ⅱ cell differentiation in fetal rhesus monkey lung by administration of EGF.Am J Physiol.1992 Mar;262(3 Pt 1):L313-21.
[23].Casalino-Matsuda SM,Monzon ME,Forteza RM.Epidermal growth factor receptor activation by epidermal growth factor mediates oxidant-induced goblet cell metaplasia in human airway epithelium.Am J Respir Cell Mol Biol.2006May;34(5):581-91.
[24].Huang BR,Cai LW,Wang X,Ma XM,Ma XL,Li JJ,et al.[Purification of recombinant hEGF expressed in yeast Pichia pastoris and the study on its characters].Zhongguo Yi Xue Ke Xue Yuan Xue Bao.2001 Apr;23(2):106-10.
[25].陈伟,付小兵,孙同柱,孙晓庆,孙鹏,赵志力.表皮细胞生长因子及其受体在难愈性溃疡组织中的表达特征.中国危重病急救医学.2003年10月:15(10):600-2.
[26].付小兵,孙同柱,孙晓庆,杨银辉,顾小曼,盛志勇.EGF和bFGF在大鼠不同发育阶段肠道定位和表达特征的比较研究.中国危重病急救医学.2001年7月:13(7):407-9.
[27].Reindel JF,Gough AW,Pilcher GD,Bobrowski WF,Sobocinski GP,de la Iglesia FA.Systemic proliferative changes and clinical signs in cynomolgus monkeys administered a recombinant derivative of human epidermal growth factor.Toxicol Pathol.2001 Mar-Apr;29(2):159-73.
[28].Xia L,Yuan YZ,Xu CD,Zhang YP,Qiao MM,Xu JX.Effects of epidermal growth factor on the growth of human gastric cancer cell and the implanted tumor of nude mice.World J Gastroenterol.2002 Jun;8(3):455-8.
[29].Fu X,Sun X,Li X,Sheng Z.Dedifferentiation of epidermal cells to stem cells in vivo.Lancet.2001 Sep 29;358(9287):1067-8.
[30].Sirisathien S,Hemandez-Fonseca H J,Brackett BG Influences of epidermal growth factor and insulin-like growth factor-Ⅰ on bovine blastocyst development in vitro.Anim Reprod Sci.2003 May 15;77(1-2):21-32.
[31].赵永健,刘群.重组人表皮生长因子治疗吸入性损伤的临床观察.中华烧伤杂志.2004年2月;20(1):47.
[32].汪涛.表皮细胞生长因子治疗吸入性损伤的临床观察.中华烧伤杂志.2003年10月;19(5):303.
[33].Li JX,Liu XS,Tang H,Zhou X,Huang YS.[Influence of some topical antibiotics and FGF2,EGF and rhGH on the biological characteristics of fibroblasts in vitro].Zhonghua Shao Shang Za Zhi.2006 Feb;22(1):33-7.
[34].Shih A,Zhang S,Cao HJ,Tang HY,Davis FB,Davis PJ,et al.Disparate effects of thyroid hormone on actions of epidermal growth factor and transforming growth factor-alpha are mediated by 3',5'-cyclic adenosine 5'-monophosphate-dependent protein kinase Ⅱ.Endocrinology.2004Apr;145(4):1708-17.
[2]. Shun-Zhen Q, Hong-Hang Z. The effects of inhaled nitric oxide on the levels of cGMP plasma and lung tissue in a canine model of smoke inhalation injury. Burns.2002 Jun;28(4):299-304.
[3]. Cox RA, Burke AS, Soejima K, Murakami K, Katahira J, Traber LD, et al.Airway obstruction in sheep with burn and smoke inhalation injuries. American journal of respiratory cell and molecular biology. 2003 Sep;29(3 Pt 1):295-302.
[4]. Westphal M, Morita N, Enkhbaatar P, Murakami K, Traber L, Traber DL.Acute effects of combined burn and smoke inhalation injury on carboxyhemoglobin formation, tissue oxygenation, and cardiac performance. Biochem Biophys Res Commun. 2004 May 7;317(3):945-9.
[5]. Pryor WA. Biological effects of cigarette smoke, wood smoke, and the smoke from plastics: the use of electron spin resonance. Free radical biology and medicine.1992 Dec;13(6):659-76.
[6]. Demling R, Ikegami K, Lalonde C. Increased lipid peroxidation and decreased antioxidant activity correspond with death after smoke exposure in the rat. The Journal of burn care and rehabilitation. 1995 Mar-Apr;16(2 Pt 1):104-10.
[7]. Demling R, Lalonde C, Picard L, Blanchard J. Changes in lung and systemic oxidant and antioxidant activity after smoke inhalation. Shock (Augusta, Ga. 1994 Feb;1(2):101-7.
[8]. Haponik EF. Clinical smoke inhalation injury: pulmonary effects. Occupational medicine (Philadelphia, Pa. 1993 Jul-Sep;8(3):430-68.
[9]. Quinn DA, Robinson D, Jung W, Hales CA. Role of sulfidopeptide leukotrienes in synthetic smoke inhalation injury in sheep. J Appl Physiol. 1990 May;68(5):1962-9.
[10]. Chung KF, Rogers DF, Barnes PJ, Evans TW. The role of increased airway microvascular permeability and plasma exudation in asthma. Eur Respir J. 1990 Mar;3(3):329-37.
[11]. Barnes PJ, Chung KF, Page CP. Inflammatory mediators of asthma: an update. Pharmacological reviews. 1998 Dec;50(4):515-96.
[12]. Soejima K, McGuire R, Snyder Nt, Uchida T, Szabo C, Salzman A, et al. The effect of inducible nitric oxide synthase (iNOS) inhibition on smoke inhalation injury in sheep. Shock (Augusta, Ga. 2000;13(4):261-6.
[13]. Murakami K, Traber DL. Pathophysiological basis of smoke inhalation injury.News Physiol Sci. 2003 Jun;18:125-9.
[14]. Enkhbaatar P, Kikuchi Y, Traber LD, Westphal M, Morita N, Maybauer MO,et al. Effect of inhaled nitric oxide on pulmonary vascular hyperpermeability in sheep following smoke inhalation. Burns. 2005 Dec;31(8):1013-9.
[15]. Abdi S, Herndon DN, Traber LD, Ashley KD, Stothert JC, Jr., Maguire J, et al. Lung edema formation following inhalation injury: role of the bronchial blood flow. J Appl Physiol. 1991 Aug;71(2):727-34.
16. Isago T, Noshima S, Traber LD, Herndon DN, Traber DL. Analysis of pulmonary microvascular permeability after smoke inhalation. J Appl Physiol. 1991 Oct;71(4):1403-8.
[17]. Basadre JO, Sugi K, Traber DL, Traber LD, Niehaus GD, Herndon DN. The effect of leukocyte depletion on smoke inhalation injury in sheep. Surgery. 1988 Aug;104(2):208-15.
[18]. Ahn SY, Sugi K, Talke P, Theissen JL, Linares HA, Traber LD, et al. Effects of allopurinol on smoke inhalation in the ovine model. J Appl Physiol. 1990 Jan;68(1):228-34.
[19]. Ambiavagar M, Chalon J, Zargham I. Tracheobronchial cytologic changes following lower airway thermal injury. A preliminary report. J Trauma. 1974 Apr,14(4):280-9.
[20]. Traber DL, Linares HA, Herndon DN, Prien T. The pathophysiology of inhalation injury~a review. Burns Incl Therm Inj. 1988 Oct;14(5):357-64.
[21]. Leal Filho MB, Morandin RC, de Almeida AR, Cambiucci EC, Metze K,Borges G, et al. Hemodynamic parameters and neurogenic pulmonary edema following spinal cord injury: an experimental model. Arquivos de neuro-psiquiatria.2005 Dec;63(4):990-6.
[22].Traber DL,Hemdon DN,Stein MD,Traber LD,Flynn JT,Niehaus GD.The pulmonary lesion of smoke inhalation in an ovine model.Circulatory shock.1986;18(4):311-23.
[23].Hubbard GB,Langlinais PC,Shimazu T,Okerberg CV,Mason AD,Jr.,Pruitt BA,Jr.The morphology of smoke inhalation injury in sheep.J Trauma.1991Nov;31(11):1477-86.
[24].Hemdon DN,Langner F,Thompson P,Linares HA,Stein M,Traber DL.Pulmonary injury in burned patients.The Surgical clinics of North America.1987Feb;67(1):31-46.
[25].Takemura R,Werb Z.Secretory products of macrophages and their physiological functions.Am J Physiol.1984 Jan;246(1 Pt 1):C1-9.
[26].Bidani A,Wang CZ,Heming TA.Early effects of smoke inhalation on alveolar macrophage functions.Burns.1996 Mar;22(2):101-6.
[27].Cohen.S.Epidermal growth factor.Nobel lecture.Biosci Rep.1986(6):1017-28.
[28].Sinha A,Nightingale J,West KP,Berlanga-Acosta J,Playford RJ.Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis.N Engl J Med.2003 Jul 24;349(4):350-7.
[29].Wilson SE,Lloyd SA.Epidermal growth factor and its receptor,basic fibroblast growth factor,transforming growth factor beta-1,and interleukin-1 alpha messenger RNA production in human corneal endothelial cells.Invest Ophthalmol Vis Sci.1991 Sep;32(10):2747-56.
[30].Tuomela T,Miettinen P,Pesonen K,Viinikka L,Perheentupa J.Epidermal growth factor in mice:effects of estradiol,testosterone and dexamethasone.Acta endocrinologica.1990 Aug;123(2):211-7.
[31].Kasselberg AG,Orth DN,Gray ME,Stahlman MT.Immunocytochemical localization of human epidermal growth factor/urogastrone in several human tissues.J Histochem Cytochem.1985 Apr;33(4):315-22.
[32].Patel JD.Role of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of bronchoalveolar carcinoma.Clinical lung cancer.2004 Dec;6Suppl 1:S43-7.
[33]. Tesfaigzi J, Johnson NF, Lechner JF. Induction of EGF receptor and erbB-2 during endotoxin-induced alveolar type II cell proliferation in the rat lung. International journal of experimental pathology. 1996 Aug;77(4):143-54.
[34]. Carpenter G, Cohen S. Epidermal growth factor. The Journal of biological chemistry. 1990 May 15;265(14):7709-12.
[35]. Abe K, Saito H. The mitogen-activated protein kinase cascade mediates neurotrophic effect of epidermal growth factor in cultured rat hippocampal neurons.Neurosci Lett. 2000 Mar 17;282(1-2):89-92.
[36]. Huang Y, Chang Y, Wang X, Jiang J, Frank SJ. Growth hormone alters epidermal growth factor receptor binding affinity via activation of extracellular signal-regulated kinases in 3T3-F442A cells. Endocrinology. 2004 Jul;145(7):3297-306.
[37]. Saito T, Okada S, Ohshima K, Yamada E, Sato M, Uehara Y, et al.Differential activation of epidermal growth factor (EGF) receptor downstream signaling pathways by betacellulin and EGF. Endocrinology. 2004 Sep;145(9):4232-43.
[38]. Khan SM, Oliver RH, Yeh J. Epidermal growth factor receptor inhibition by tyrphostin 51 induces apoptosis in luteinized granulosa cells. J Clin Endocrinol Metab.2005 Jan;90(1):469-73.
[39]. Sheng G, Bernabe KQ, Guo J, Warner BW. Epidermal growth factor receptor-mediated proliferation of enterocytes requires p21wafl/cipl expression.Gastroenterology. 2006 Jul;131(1):153-64.
[40]. Horbar JD, Carpenter JH, Buzas J, Soil RF, Suresh G, Bracken MB, et al. Timing of initial surfactant treatment for infants 23 to 29 weeks' gestation: is routine practice evidence based? Pediatrics. 2004 Jun;113(6):1593-602.
[41]. Clegg GR, Tyrrell C, McKechnie SR, Beers MF, Harrison D, McElroy MC.Coexpression of RTI40 with alveolar epithelial type II cell proteins in lungs following injury: identification of alveolar intermediate cell types. Am J Physiol Lung Cell Mol Physiol. 2005 Sep;289(3):L382-90.
[42]. Guazzi M. Alveolar-capillary membrane dysfunction in heart failure:evidence of a pathophysiologic role. Chest. 2003 Sep;124(3):1090-102.
[43]. Tesfaigzi Y. Roles of apoptosis in airway epithelia. Am J Respir Cell Mol Biol. 2006 May;34(5):537-47.
[44]. McDowell EM, Becci PJ, Schurch W, Trump BF. The respiratory epithelium.VII. Epidermoid metaplasia of hamster tracheal epithelium during regeneration following mechanical injury. Journal of the National Cancer Institute. 1979 Apr;62(4):995-1008.
[45]. Fan WH, Lu YL, Deng F, Ge XM, Liu S, Tang PH. EGFR antisense RNA blocks expression of the epidermal growth factor receptor and partially reverse the malignant phenotype of human breast cancer MDA-MB-231 cells. Cell research.1998 Mar;8(1):63-71.
[46]. Kim JS, McKinnis VS, Nawrocki A, White SR. Stimulation of migration and wound repair of guinea-pig airway epithelial cells in response to epidermal growth factor. Am J Respir Cell Mol Biol. 1998 Jan;18(1):66-74.
[47]. Zahm JM, Kaplan H, Herard AL, Doriot F, Pierrot D, Somelette P, et al. Cell migration and proliferation during the in vitro wound repair of the respiratory epithelium. Cell Motil Cytoskeleton. 1997;37(1):33-43.
[48]. Erjefalt JS, Erjefalt I, Sundler F, Persson CG In vivo restitution of airway epithelium. Cell Tissue Res. 1995 Aug;281(2):305-16.
[49]. White SR DD, Rabe KF, et al. Role of very late adhesion integrins in mediating repair of human airway epithelial cell monolayers after mechanical injury.Am J Respir Cell Mol Biol. 1999(20):787-96.
[50]. Jost M, Kari C, Rodeck U. The EGF receptor - an essential regulator of multiple epidermal functions. Eur J Dermatol. 2000 Oct-Nov;10(7):505-10.
[51]. Tyner JW, Kim EY, Ide K, Pelletier MR, Roswit WT, Morton JD, et al.Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13 transdifferentiation signals. J Clin Invest. 2006 Feb;116(2):309-21.
[52]. Raaberg L, Nexo E, Buckley S, Luo W, Snead ML, Warburton D. Epidermal growth factor transcription, translation, and signal transduction by rat type II pneumocytes in culture. Am J Respir Cell Mol Biol. 1992 Jan;6(l):44-9.
[53]. Plopper CG, St George JA, Read LC, Nishio SJ, Weir AJ, Edwards L, et al.Acceleration of alveolar type II cell differentiation in fetal rhesus monkey lung by administration of EGF.Am J Physiol.1992 Mar;262(3 Pt 1):L313-21.
[54].Al-Salmi QA,Walter JN,Colasurdo GN,Sockrider MM,Smith EO,Takahashi H,et al.Serum KL-6 and surfactant proteins A and D in pediatric interstitial lung disease.Chest.2005 Jan;127(1):403-7.
[55].Clark H,Reid K.The potential of recombinant surfactant protein D therapy to reduce inflammation in neonatal chronic lung disease,cystic fibrosis,and emphysema.Arch Dis Child.2003 Nov;88(11):981-4.
[56].Kattwinkel J.Synthetic surfactants:the search goes on.Pediatrics.2005Apr;115(4):1075-6.
[57].Gratzner HG.Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine:A new reagent for detection of DNA replication.Science(New York,NY.1982 Oct 29;218(4571):474-5.
[58].Barrow RE,Wang CZ,Evans MJ,Herndon DN.Growth factors accelerate epithelial repair in sheep trachea.Lung.1993;171(6):335-44.
[59].Garat C,Meignan M,Matthay MA,Luo DF,Jayr C.Alveolar epithelial fluid clearance mechanisms are intact after moderate hyperoxic lung injury in rats.Chest.1997 May;111(5):1381-8.
[60].Montaner JS,Tsang J,Evans KG,Mullen JB,Bums AR,Walker DC,et al.Alveolar epithelial damage.A critical difference between high pressure and oleic acid-induced low pressure pulmonary edema.The Journal of clinical investigation.1986 Jun;77(6):1786-96.
[61].Borok Z,Hami A,Danto SI,Lubman RL,Kim KJ,Crandall ED.Effects of EGF on alveolar epithelial junctional permeability and active sodium transport.Am J Physiol.1996 Apr;270(4 Pt 1):L559-65.
[62].Skou JC.The identification of the sodium pump.Biosci Rep.2004Aug-Oct;24(4-5):436-51.
[63].Blanco G.Mercer RW.Isozymes of the Na-K-ATPase:heterogeneity in structure,diversity in function.Am J Physiol.1998 Nov;275(5 Pt 2):F633-50.
[64].柳琪林,胡森,陆江阳,王谊冰,杨毅,盛志勇.表皮细胞生长因子对吸入性损伤大鼠肺泡Ⅱ型细胞增殖和肺水转运的作用.中国危重病急救医学.2002年12月:14(12):719-22.
[65]. Sznajder JI, Ridge KM, Yeates DB, Ilekis J, Olivera W. Epidermal growth factor increases lung liquid clearance in rat lungs. J Appl Physiol. 1998 Sep;85(3):1004-10.
[66]. Sibille Y, Reynolds HY. Macrophages and polymorphonuclear neutrophils in lung defense and injury. The American review of respiratory disease. 1990 Feb;141(2):471-501.
[67]. Berman JS, Beer DJ, Theodore AC, Kornfeld H, Bernardo J, Center DM.Lymphocyte recruitment to the lung. The American review of respiratory disease.1990 Jul;142(1):238-57.
[68]. Beutler BA, Milsark IW, Cerami A. Cachectin/tumor necrosis factor:production, distribution, and metabolic fate in vivo. J Immunol. 1985 Dec;135(6):3972-7.
[69]. Vassalli P. The pathophysiology of tumor necrosis factors. Annual review of immunology. 1992;10:411-52.
[70]. Zhang K, Gharaee-Kermani M, McGarry B, Remick D, Phan SH.TNF-alpha-mediated lung cytokine networking and eosinophil recruitment in pulmonary fibrosis. J Immunol. 1997 Jan 15;158(2):954-9.
[71]. Imrich A, Ning YY, Koziel H, Coull B, Kobzik L. Lipopolysaccharide priming amplifies lung macrophage tumor necrosis factor production in response to air particles. Toxicology and applied pharmacology. 1999 Sep 1;159(2): 117-24.
[72]. Conroy DM, Francischi JN, Sirois P. Effect of tumor necrosis factor receptor binding protein on cell infiltration induced by lipopolysaccharide and Sephadex beads in guinea pig lung. Inflammation. 1995 Apr;19(2):233-43.
[73]. Whitsett JA, Clark JC, Wispe JR, Pryhuber GS. Effects of TNF-alpha and phorbol ester on human surfactant protein and MnSOD gene transcription in vitro. The American journal of physiology. 1992 Jun;262(6 Pt 1):L688-93.
[74]. Li X, Xing XM, Zhang JS, Tan YR. [Effect of vasoactive intestinal peptide and epidermal growth factor on the adhesion of eosinophils to bronchial epithelial cells]. Zhong nan da xue xue bao Yi xue ban = Journal of Central South University.2006 Oct;31(5):772-5,81.
[75]. Casaco A, Ledon N, Gonzalez A, Merino N, Perez R. Topical anti-inflammatory activity of human recombinant epidermal growth factor.Skin Pharmacol Appl Skin Physiol.1999 Jan-Apr;12(1-2):79-84.
[76].Rocourt DV,Mehta VB,Besner GE.Heparin-binding EGF-like growth factor decreases inflammatory cytokine expression after intestinal ischemia/reperfusion injury.J Surg Res.2007 May 15;139(2):269-73.
[77].Gospodarowicz D,Mescher AL,Birdwell CR.Control of cellular proliferation by the fibroblast and epidermal growth factors.National Cancer Institute monograph.1978 May(48):109-30.
[78].赵永健,刘群.重组人表皮生长因子治疗吸入性损伤的临床观察.中华烧伤杂志.2004年2月:20(1):47.
[79].汪涛.表皮细胞生长因子治疗吸入性损伤的临床观察.中华烧伤杂志.2003年10月;19(5):303.
[80].赵英,廖立新,杨大华,李国辉.表皮细胞生长因子对烧伤合并吸入性损伤的治疗作用.第二军医大学学报.2005年9月;26(9):1066-7.
[1].Cohen S.Nobel lecture.Epidermal growth factor.Biosci Rep.1986Dec;6(12):1017-28.
[2].Sinha A,Nightingale J,West KP,Berlanga-Acosta J,Playford RJ.Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis.N Engl J Med.2003 Jul 24;349(4):350-7.
[3].G.R.Clegg CT,S.R.McKechnie,M.F.Beers,D.Harrison and M.C.McElroy.Coexpression of RTI40 with alveolar epithelial type Ⅱ cell proteins in lungs following injury:identification of alveolar intermediate cell types.Am J Physiol Lung Cell Mol Physiol,September 1.2005;289(3):L382-L90.
[4].Guazzi M.Alveolar-capillary membrane dysfunction in heart failure:evidence of a pathophysiologic role.Chest.2003 Sep;124(3):1090-102.
[5].Puddicombe SM,Torres-Lozano C,Richter A,Bucchieri F,Lordan JL,Howarth PH,et al.Increased expression of p21(waf)cyclin-dependent kinase inhibitor in asthmatic bronchial epithelium.Am J Respir Cell Mol Biol.2003Jan;28(1):61-8.
[6].Puddicombe SM,Polosa R,Richter A,Krishna MT,Howarth PH,Holgate ST,et al.Involvement of the epidermal growth factor receptor in epithelial repair in asthma.Faseb J.2000 Jul;14(10):1362-74.
[7].Jost M,Kari C,Rodeck U.The EGF receptor-an essential regulator of multiple epidermal functions.Eur J Dermatol.2000 Oct-Nov;10(7):505-10.
[8].Burgel PR,Nadel JA.Roles of epidermal growth factor receptor activation in epithelial cell repair and mucin production in airway epithelium.Thorax.2004Nov;59(11):992-6.
[9].Tyner JW,Kim EY,Ide K,Pelletier MR,Roswit WT,Morton JD,et al.Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13transdifferentiation signals.J Clin Invest.2006 Feb;116(2):309-21.
[10].Wang HQ,Quan T,He T,Franke TF,Voorhees JJ,Fisher GJ.Epidermal growth factor receptor-dependent,NF-kappaB-independent activation of the phosphatidylinositol 3-kinase/Akt pathway inhibits ultraviolet irradiation-induced caspases-3,-8,and -9 in human keratinocytes.J Biol Chem.2003 Nov 14;278(46):45737-45.
[11].Allan LA,Morrice N,Brady S,Magee G,Pathak S,Clarke PR.Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK.Nat Cell Biol.2003Jul;5(7):647-54.
[12].Abe K,Saito H.The mitogen-activated protein kinase cascade mediates neurotrophic effect of epidermal growth factor in cultured rat hippocampal neurons.Neurosci Lett.2000 Mar 17;282(1-2):89-92.
[13].Huang Y,Chang Y,Wang X,Jiang J,Frank SJ.Growth hormone alters epidermal growth factor receptor binding affinity via activation of extracellular signal-regulated kinases in 3T3-F442A cells.Endocrinology.2004Jul;145(7):3297-306.
[14].Saito T,Okada S,Ohshima K,Yamada E,Sato M,Uehara Y,et al.Differential activation of epidermal growth factor(EGF)receptor downstream signaling pathways by betacellulin and EGF.Endocrinology.2004Sep;145(9):4232-43.
[15].Khan SM,Oliver RH,Yeh J.Epidermal growth factor receptor inhibition by tyrphostin 51 induces apoptosis in luteinized granulosa cells.J Clin Endocrinol Metab.2005 Jan;90(1):469-73.
[16].Sheng G,Bernabe KQ,Guo J,Warner BW.Epidermal growth factor receptor-mediated proliferation of enterocytes requires p21waf1/cip1 expression.Gastroenterology.2006 Jul;131(1):153-64.
[17].Functional genomics of lung disease.Second annual Pittsburgh International Lung Conference,October 2003.Am J Respir Cell Mol Biol.2004 Aug;31(2Suppl):S1-81.
[18].Kim JS,McKinnis VS,Nawrocki A,White SR.Stimulation of migration and wound repair of guinea-pig airway epithelial cells in response to epidermal growth factor.Am J Respir Cell Mol Biol.1998 Jan;18(1):66-74.
[19].White SR,Dorscheid DR,Rabe KF,Wojcik KR,Hamann KJ.Role of very late adhesion integrins in mediating repair of human airway epithelial cell monolayers after mechanical injury.Am J Respir Cell Mol Biol.1999 Apr;20(4):787-96.
[20].柳琪林,胡森,陆江阳,王谊冰,杨毅,盛志勇.表皮细胞生长因子对吸入性损伤大鼠肺泡Ⅱ型细胞增殖和肺水转运的作用.中国危重病急救医学.2002年12月:14(12):719-22.
[21].Nielsen HC,Martin A,Volpe MV,Hatzis D,Vosatka RJ.Growth factor control of growth and epithelial differentiation in embryonic lungs.Biochem Mol Med.1997 Feb;60(1):38-48.
[22].Plopper CG,St George JA,Read LC,Nishio SJ,Weir AJ,Edwards L,et al.Acceleration of alveolar type Ⅱ cell differentiation in fetal rhesus monkey lung by administration of EGF.Am J Physiol.1992 Mar;262(3 Pt 1):L313-21.
[23].Casalino-Matsuda SM,Monzon ME,Forteza RM.Epidermal growth factor receptor activation by epidermal growth factor mediates oxidant-induced goblet cell metaplasia in human airway epithelium.Am J Respir Cell Mol Biol.2006May;34(5):581-91.
[24].Huang BR,Cai LW,Wang X,Ma XM,Ma XL,Li JJ,et al.[Purification of recombinant hEGF expressed in yeast Pichia pastoris and the study on its characters].Zhongguo Yi Xue Ke Xue Yuan Xue Bao.2001 Apr;23(2):106-10.
[25].陈伟,付小兵,孙同柱,孙晓庆,孙鹏,赵志力.表皮细胞生长因子及其受体在难愈性溃疡组织中的表达特征.中国危重病急救医学.2003年10月:15(10):600-2.
[26].付小兵,孙同柱,孙晓庆,杨银辉,顾小曼,盛志勇.EGF和bFGF在大鼠不同发育阶段肠道定位和表达特征的比较研究.中国危重病急救医学.2001年7月:13(7):407-9.
[27].Reindel JF,Gough AW,Pilcher GD,Bobrowski WF,Sobocinski GP,de la Iglesia FA.Systemic proliferative changes and clinical signs in cynomolgus monkeys administered a recombinant derivative of human epidermal growth factor.Toxicol Pathol.2001 Mar-Apr;29(2):159-73.
[28].Xia L,Yuan YZ,Xu CD,Zhang YP,Qiao MM,Xu JX.Effects of epidermal growth factor on the growth of human gastric cancer cell and the implanted tumor of nude mice.World J Gastroenterol.2002 Jun;8(3):455-8.
[29].Fu X,Sun X,Li X,Sheng Z.Dedifferentiation of epidermal cells to stem cells in vivo.Lancet.2001 Sep 29;358(9287):1067-8.
[30].Sirisathien S,Hemandez-Fonseca H J,Brackett BG Influences of epidermal growth factor and insulin-like growth factor-Ⅰ on bovine blastocyst development in vitro.Anim Reprod Sci.2003 May 15;77(1-2):21-32.
[31].赵永健,刘群.重组人表皮生长因子治疗吸入性损伤的临床观察.中华烧伤杂志.2004年2月;20(1):47.
[32].汪涛.表皮细胞生长因子治疗吸入性损伤的临床观察.中华烧伤杂志.2003年10月;19(5):303.
[33].Li JX,Liu XS,Tang H,Zhou X,Huang YS.[Influence of some topical antibiotics and FGF2,EGF and rhGH on the biological characteristics of fibroblasts in vitro].Zhonghua Shao Shang Za Zhi.2006 Feb;22(1):33-7.
[34].Shih A,Zhang S,Cao HJ,Tang HY,Davis FB,Davis PJ,et al.Disparate effects of thyroid hormone on actions of epidermal growth factor and transforming growth factor-alpha are mediated by 3',5'-cyclic adenosine 5'-monophosphate-dependent protein kinase Ⅱ.Endocrinology.2004Apr;145(4):1708-17.