维持血液透析患者血小板凝血酶受体的临床研究及中西医结合治疗
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
第一部分维持血液透析患者血小板凝血酶受体的表达
     目的:观察维持血液透析患者血小板蛋白酶激活受体1(PAR1)、蛋白酶激活受体4(PAR4)和膜糖蛋白Iba (GPIba)的表达与正常人之间的差异。
     方法:采用流式细胞术检测PAR1,PAR4和GPIba的表达,采用比浊法检测其血小板最大聚集率(MAR)。
     结果:维持透析患者血小板表面GPIba表达略低于对照组,PAR1表达升高(P<0.05),血小板最大聚集率降低(P<0.05);相关性分析显示PAR1的表达和血液透析频率之间存在明显正相关(r=0.601,P<0.05)。
     结论:PAR1作为具有高亲和力的凝血酶受体,在维持透析患者体内的过度表达,导致血小板聚集功能增强,可能是该类患者心脑血管事件频发的主要原因之一。
     第二部分参芎葡萄糖注射液对肾病终末期维持血液透析患者血小板凝血酶受体1和受体4的影响
     目的:观察肾病终末期维持血液透析患者使用参芎葡萄糖注射液对血小板凝血酶受体1(PAR1)和受体4(PAR4)表达的影响。
     方法:选取肾病终末期长期透析患者86例,使用参芎葡萄糖注射液,7天为一个疗程,连续使用2个疗程。其他治疗方案不变。使用流式细胞仪检测治疗前后PAR1和PAR4的表达,采用比浊法检测其血小板最大聚集率(MAR),同时检测肾功能。并与正常对照组比较。
     结果:治疗前肾病终末期长期透析患者PAR1、PAR4表达和血小板最大聚集率明显高于对照组(P=0.001,P=0.006,P=0.008);参芎葡萄糖注射液治疗后,除了PAR4(P=0.067),以上指标较治疗前均明显下降(P=0.036,P=0.046),虽仍高于对照组,但无明显统计学意义。
     结论:(1)血小板PAR1在肾病终末期长期透析患者体内的过度表达,从而导致血小板聚集功能增强,这可能是肾病终末期长期透析患者存在血栓风险的原因之一;(2)参芎葡萄糖注射液可降低患者PAR1、PAR4的表达,有效改善血小板功能,调节血小板活性。
Part one Levels of main platelet thrombin receptors in chronic haemodialysis patients
     Objective:To investigate the expression of platelet membrane receptors proteinase activated receptor-1(PARl), proteinase activated receptor-4(PAR4) and glycoprotein Iba (GPIba) in patients on chronic haemodialysis (HD).
     Methods:Flow cytomery was used to assess the expression of PARl, PAR4and GPIba levels on the platelet surface. Platelet reactivity was assessed by ADP-stimulated aggregation. The results were expressed as the maximal platelet aggregation rate (MAR).
     Results:The expression of GPIba was a little lower, the PARl percentage was higher (P<0.05) and the platelet MAR(%) in the chronic haemodialysis group was obviously lower than in the control subjects (P <0.05). There was a positive relationship between PARl levels and the months of HD(r=0.601,P<0.05).
     Conclusion:The presence of a high PARl level and more cardiovascular and cerebrovascular events in the HD group may indicate that the increase of platelet PARl level is a risk marker in HD patients.
     Part two Effects of Salvia Miltiorrhiza Liguspyragine Hydrochlorid and Glucose Injection on the levels of main platelet thrombin receptors in chronic haemodialysis patients
     Objective:To investigate the effects of Salvia Miltiorrhiza Liguspyragine Hydrochlorid and Glucose Injection(参芎葡萄糖注射液,SLGI) on the expression of platelet membrane receptors proteinase activated receptor-1(PARl) and proteinase activated receptor-4(PAR4) in end-stage renal disease (ESRD) patients on chronic haemodialysis (HD).
     Methods:Eighty-six patients in ESRD with HD were treated with SLGI,7days as one therapeutic course, for2successive courses. The previous therapies remained unchanged. Flow cytometry was used to detect the expression of platelet PARl and PAR4in patients, and turbidity method was used to determine the platelet maximum aggregation rate (MAR), meanwhile the renal function was measured. The final data were compared with those before the treatment, and with those in the normal control group (54healthy subjects).
     Results:Compared with the normal control group, expressions of PARl and PAR4, and platelet MAR in ESRD patients on HD were significantly higher (P=0.001, P=0.006, P=0.008) before the treatment; after the treatment with SLGI, the above indexes in patients were remarkably decreased (P-0.036, P=0.046), except PAR4(P=0.067), but still higher than those in the normal control group, however, it was not statistically significant.
     Conclusion:(1) The overexpressions of PAR1and PAR4lead to platelet aggregation increased and this might be one of the reasons for the thrombic events in ESRD patients on HD.(2) SLGI was able to down-regulate expressions of PAR1and PAR4in ESRD patients on HD, improve platelet function and regulate platelet activation.
引文
1. Levey AS, Eckardt KU, Tsukamoto Y, et al. Definition and classification of chronic kidney disease:a position statement from Kidney Disease:Improving Global Outcomes (KD IGO). Kidney Int,2005,67(6):2089-2100.
    2.刘加林,黄霞,程世平,等。血液透析对老年慢性肾功能衰竭患者治疗分析。贵州医药,2003,27(6):525-526.
    3. Ji Daxi, Gong Dehua, Xie Honglang, et al. A retrospective study of continuous renal replacement therapy versus intermittent hemodialysis in severe acute renal failure. Chin Med J(Engl),2001,114(11):1157-1161.
    4.马祖等,郑智华,张涤华,等。血液透析和腹膜透析患者生存质量的多中心调查。中华肾脏病杂志,2004,20(6):400-405。
    5. Meguid El Nahas A, Bello AK. Chronic kidney disease:the global challenge. Lancet, 2005,365(9456):331-340.
    6. Stevens LA, Levey AS. Chronic kidney disease in the elderly-how to assess risk. N Engl Jmed,2005,352(20):2122-2124.
    7. Coresh J, Astor BC, Greene T, et al. Prevalence of chronic kidney disease and decreased kidney function in the adult US population:Third National Health and Nutrition Examination Survey. Am J Kidney Dis,2003,41(1):1-12.
    8.季大玺。规律性血液透析病人的心血管问题。中国实用内科杂志,2004,24(7):387-388.
    9.孙世泽,李静红。基层医院血液透析患者死亡原因分析及预防措施。中国社区医师,2010,12(21):38.
    10. Xue JL, Ma JZ, Louis TA, et al. Forecast of the number of patients with end-stage renal disease in the United States to the year 2010 J Am Soc Nephrol,2001,12(12):2753-2758.
    11.张路霞,左力,徐国宾,等.北京市石景山地区中老年人群中慢性肾脏病的流行病学研究.中华肾脏病杂志,2006,22(2):67-71.
    12.赵静瑜,吴际,王乃平。维持性血液透析患者应用不同血液净化方式对残余肾功能影响的临床研究。中国血液净化,2011,10(2):71-73.
    13.候永梅,胡佩斌,梁燕萍,等。肾移植前后实施维持性血液透析患者生活质量的评估及其影响因素。中国组织工程研究与临床康复,2009,10(29):8721-8725.
    14.郑杨,张琪。中医治疗慢性肾衰竭的思路和方法。中国中医基础医学杂志,2004,10(8):599-600.
    15杨丽,梅长林。解读美国糖尿病及慢性肾脏病临床实践指南。中华肾脏病杂志,2007,23(10):681-684.
    16.叶凤,梁海琴。413例慢性肾功能衰竭的病因分析.中国热带医学,2007,7(10):1818-18 19.
    17.赵卫佐。212例维持性血透患者病因分析。中国医学创新,2010,7(13):72-73.
    18.毕礼明,马济佩。中医治疗慢性肾脏病临床研究的规范性探讨。江苏中医药,2009,41(3): 15-16.
    19.王永钧,周柳沙。进一步提高慢性肾脏病的辨证水平。中国中西医结合肾病杂志。2010:11(2):95-97.
    20.刘军民,张欣洲。足细胞损伤、肾干-祖细胞枯竭与慢性肾脏病进展机制。中华肾脏病杂志,2011,27(12):945-948.
    21.陶兴,孙伟。慢性肾脏病浊毒病机与治法探讨。江苏中医药,2008,40(9):15-16.
    22.王素芹。从痰论治慢性肾脏病。辽宁中医药大学学报,2008,10(6):27-28.
    23.李靖,解红霞,戴先文,等。慢性肾脏病分期的中医证候专家调查分析报告。中国中西医结合肾病杂志,2009,10(12):1089-1091.
    24.刘章锁,王沛。K/DOQI指南关于慢性肾脏病分期的临床指导意义。中国实用内科杂志,2008,28(1):21-24.
    25.全球提高肾脏病预后组织。全球提高肾脏病预后组织慢性肾脏病-矿物质和骨异常诊断、评价、预防和治疗的临床实践指南。中华内科杂志,2009,48(12):1068-1070.
    26.毕礼明,马济佩。中医治疗慢性肾脏病临床研究的规范性探讨。全国中西医结合肾脏病南京论坛,2008,189-192。
    27.吕小波,尹鸿萍,李海涛,等.虫草多糖对大鼠肾脏冷冻诱发慢性肾功能衰竭的治疗作用。药学进展,2007,31(7):314-319.
    28.邓跃毅,陈以平,贺学林,等。冬虫夏草制剂延缓慢性肾衰竭的机理研究。中国中西医结合肾病杂志,2001,2(7):381-383.
    29.傅余芹。冬虫夏草制剂对慢性肾功能不全患者T细胞亚群的影响.深圳中西医结合杂志,2003,13(1):21-26.
    30.王志红.大黄治疗慢性肾功能衰竭172例疗效分析.中国综合临床,2005,21(4):332-333.
    31郭伟。大黄和巯甲丙脯酸治疗慢性肾衰的临床评价。第三届全国铁路肾脏病学术交流会暨99’海峡两岸肾病研讨会。1999.
    32.刘志红,李颖健,章精,等.转化生长因子及大黄酸对肾小球系膜细胞葡萄糖转运蛋白功能的影响.中华医学杂志,1999,79(10):780-783.
    33.郭啸华,刘志红,戴春笋,等.大黄酸抑制TGF 诱导的肾小管上皮细胞肥大及细胞外基质产生.肾脏病与透析肾移植杂志,2001, 10(2):101-105.
    34.周钦,曹文富,李荣亨.大剂量黄芪注射液对慢性肾功能不全患者血浆、尿液内皮素的影响.中国中药杂志,2001,26(3):200-202.
    35.左川,谢席胜,邱红渝,等。黄芪对单侧输尿管梗阻大鼠肾间质纤维化的作用研究。现代预防医学,2008,35(4):784-787.
    36. Yu Ling, Lu Youyong, Li Lingzi, et al. Identification of a gene associated with astragalus and angelica's renal protective effects by silver staining mRNA differential display. Chin Med J (Engl),2002,115(6):923-927.
    37.李洪清,徐学明。丹参对慢性肾功能不全患者白细胞介素-6和肿瘤坏死因子的影响。临床内科杂志,2002,19(6):470-471.
    38.徐曼,王逸平,孙伟康,等。丹参多酚酸盐对大鼠慢性肾衰时肾功能及内源性内皮素释放的影响.中国药理学与毒理学杂志,2001,15(1):39-42.
    39.单福军,孙铁忠,齐卡,等。川芎素注射液治疗慢性肾功能衰竭482例.现代中西医结合杂志,2004,13(23):3139-3140.
    40孙林,易著文,虞佩兰。川芎嗪对人胚肾系膜细胞增殖的影响及其机理探讨。中国中西医结合杂志,1995,15(3):134-136.
    41.苏春梅,梁翠茵,王姝,等。川芎嗪对大鼠实验性慢性肾功能衰竭的治疗作用。贵州医药,2004,28(2):122-123.
    42.刘宝义,李英。黄芪川芎对实验性糖尿病大鼠肾脏形态学的影响。中国中西医结合肾脏杂志,2003,4(6):323-325.
    43.唐锦辉,徐钦儒,刘桐林,等。银杏叶防治大鼠肾小球硬化及肾小管-间质损害的实验研究。中华肾脏病杂志,1998,14(3):174-176.
    44.曹灵,孙兴旺,邹德平,等。丹红注射液治疗慢性肾功能衰竭氮质血症期疗效观察。中国现代药物应用,2007,1(1):19-20.
    45.陈强,刘立萍。灯盏细辛注射液联合百令胶囊治疗慢性肾功能衰竭的临床观察。中国社区医师(医学专业半月刊),2008,10(4):61.
    46.潘慧娟。百令胶囊治疗慢性肾衰竭临床观察。现代医药卫生,2007,23(3):345-346.
    47.汤水福,洪钦国,陈刚毅。尿毒清胶囊治疗慢性肾功能衰竭56例临床研究。新中医,2008,40(1):35-37.
    48.徐晓祥,汪汉东,周忠荣,等。维持性血液透析患者185例常见并发症的原因分析。中国医学创新,2011,8(25):142-143.
    49.杨光,邢昌赢,刘佳,等。维持性血液透析住院患者临床特征分析。临床内科杂志,2011,28(7):467-469.
    50. Smith FB, Rumley A, Lee AJ, et al. Haemostatic factors and prediction of ischaemic heart disease and stroke in claudicants. Br J Haematol, 1998,100(4):758-763.
    51. Qin Y, Shen L, Lu FR, et al. Effect of Xiaoyu Zhixue Tablet on the expression of platelet membrane glycoprotein I b/IX/V complex in patients with chronic renal failure. Chin J Integr Med,2008,14(2):83-87.
    52. Di Minno G, Cerbone A, Usberti M, et al. Platelet dysfunction in uremia. II. Correction by arachidonic acid of the impaired exposure of fibrinogen receptors by adenosine diphosphate or collagen. J Lab Clin Med, 1986,108(3):246-252.
    53. Gralnick HR, McKeown LP, Williams SB, et al. Plasma and platelet von Willebrand factor defects in uremia. Am J Med,1988,85(6):806-810.
    54. Benigni A, Livio M, Dodesini P, et al. Inhibition of human platelet aggregation by parathyroid hormone. Is cyclic AMP implicated? Am J Nephrol,1985,5(4):243-247.
    55. Kyrle PA, Stockenhuber F, Brenner B, et al. Evidence for an increased generation of prostacyclin in the microvasculature and an impairment of the platelet alpha-granule release in chronic renal failure. Thromb Haemost,1988, 60(2):205-208.
    56. Covic L, Gresser AL, Kuliopulos A. Biphasic kinetics of activation and signaling for PAR1 and PAR4 thrombin receptors in platelets. Biochemistry, 2000,39(18):5458-5467.
    57. Shapiro MJ, Weiss EJ, Faruqi TR, et al. Protease-activated receptors 1 and 4 are shut off with distinct kinetics after activation by thrombin. J Biol Chem,2000,275(33):25216-25221.
    58. Xu WF, Andersen H, Whitntore T, et al. Cloning and characterization of human protease-activated receptor 4 [J]. Biochenristry,1998,95:6642.
    59. Coughlin SR, Protease-activated receptore and platelet function [J]. Thromb Harmosl,1999,82:353-356.
    60. Molino M, Bainton DF, Hoxie JA, et al. Thrombin receptore on human platelets. Initial localization and subaequent redistribution during platelet activation. [J]. J Biol Chem,1997,272:6011-6017.
    61. Connolly AJ, Ishihara H, Kahn ML, et al. Role of the thrombin receptor in development and evidence for a second receptor [J]. Nature,1996,381: 516-519.
    62. Ishihara H, Connolly AJ, Zeng D, et al. Protease-activated receptor 3 is a second thrombin recdptor in humans [J]. Nature,1997,356:502.
    63. Molino M, Woolkalis MJ, Reavey-Cantwell J, et al. Endothelial cell thrombin receptors and PAR-2. Two protease-activated receptors located in a single cellular envircomment [J]. J Bio Chem,1997,272:11133.
    64. Ishii K, Gerszten R, Zheng YW. Determinants of thrombin receptor cleavage. Receptor donasins involved, specificity, and rold of the P3 aspartate [J]. J Biol Chem,1995,270:16435-16440.
    65. Jarmidson GA. Pathophysiology of paltelet thrombin receptors [J]. Thromb heamoet,1997,78:242-246.
    66.任志强,王长美。徐锡兰治疗慢性肾衰竭经验.山东中医药大学学报,2005,29(2):123-124.
    67.李素云,龚伟峰。化瘀行水验方延缓慢性肾功能衰竭进展的临床观察。四川中医,2007,25(4):48-49.
    68. Yang HX, Jiang HB. Clinical observation of combination of danshen and chuanxiongqin injection and astragali injection in patients with stable angina pectoris. J. Beth. Military Med,2008,3.
    69. Li S, Wan L. Experimental study on the preventive mechanism of salviae miltiorrhizae against atherosclerosis in rabbits models. J Huazhong Univ Sci Technolog Med Sci,2004,24(3):233-235.
    70.王艳,李岩。丹参川芎嗪注射液治疗缺血性结肠炎的疗效观察。胃肠病学和肝病学杂志,2009,18(07):646-648
    71. Che XW, Zhang Y, Wang H, et al. Effect of ligustrazine injection on levels of interleukin-4 and interferon-gamma in patients with bronchial asthma. Chin J Integr Med,2008,14(3):217-220.
    1. Yu XQ, Wei JL. Kidney disease in China:recent progress and prospects. Chin Med J, 2009,122:2048-2053.
    2. Wang SX, Li H. Salmon calcitonin in prevention of osteoporosis in maintenance dialysis patients. Chin Med J,2008,121:1280-1284.
    3. Hou FF. Cardiovascular risk in Chinese patients with chronic kidney diseases:where do we stand? Chin Med J,2005,118:883-886.
    4. Wyant TL, Smith PC, Brown B, et al. Whole blood microvolume laser scanning cytometry for monitoring resting and activated platelets. Platelets,2001,12:309-318.
    5. Wang HY. Nephrology.2 nd ed. Beijing:People's Medical Publishing House. 1997:243-277.
    6. Linden M D, Frelinger A L,3rd, Barnard M R. Application of flow cytometry to platelet disorders. Semin Thromb Hemost,2004,30(5):501-511.
    7. Adam F, Bouton MC, Huisse MG, et al. Thrombin interaction with platelet membrane glycoprotein Ib alpha. Trends Mol Med,2003,9:461-464.
    8.秦铀,沈霖,卢芙蓉,等。慢性肾功能衰竭患者血小板膜糖蛋白I b/IX/V复合物表达的研究。实用医学杂志,2008,24(1):37-39。
    9. Diaz-Ricart M, Estebanell E, Cases A, et al. Abnormal platelet cytoskeletal assembly in hemodialyzed patients results in deficient tyrosine phosphorylation signaling. Kidney Int,2000,57:1905-1914.
    10. Nangaku M, Nishi H, Miyata T. Role of chronic hypoxia and hypoxia inducible factor in kidney disease. Chin Med J,2008,121:257-264.
    11. Hou FF. Pharmacological intervention of hypertension in proteinuric chronic kidney disease:how and what? Chin Med J,2008,121:840-843.
    12. Li Y, Shen L, Chen R, et al. Levels of main platelet thrombin receptors in older chronic haemodialysis patients. Chin Med J (Engl),2010,123(17):2495-2496.
    1. Boccardo P, Remuzzi G, Galbusera M. Platelet dysfunction in renal failure. Semin Thromb Hemost,2004,30(5):579-589.
    2. Li Y, Shen L, Chen R,et al. Levels of main platelet thrombin receptors in older chronic haemodialysis patients. Chin Med J (Engl),2010,123(17):2495-2496.
    3. Moal V, Brunet P, Dou L, et al. Impaired expression of glycoproteins on resting and stimulated platelets in uraemic patients. Nephrol Dial Transplant,2003,18(9):1834-1841.
    4. Wang HY. Nephropathy.2nded. Beijing:People's Medical Publishing,1996,1385. Medical Publishing House,1996:1385.
    5. Rink TJ, Sage SO. Calcium signaling in human platelets. Annu Rev Physiol, 1990,52:431-449.
    6. Wyant TL, Smith PC, Brown B, et al. Whole blood microvolume laser scanning cytometry for monitoring resting and activated platelets. Platelets,2001,12(5):309-318.
    7. Smith FB, Rumley A, Lee AJ, et al. Haemostatic factors and prediction of ischaemic heart disease and stroke in claudicants. Br J Haematol,1998,100(4):758-763.
    8. Qin Y, Shen L, Lu FR, et al. Effect of Xiaoyu Zhixue Tablet on the expression of platelet membrane glycoprotein I b/IX/V complex in patients with chronic renal failure. Chin J Integr Med,2008,14(2):83-87.
    9. Di Minno G, Cerbone A, Usberti M, et al. Platelet dysfunction in uremia. II. Correction by arachidonic acid of the impaired exposure of fibrinogen receptors by adenosine diphosphate or collagen. J Lab Clin Med,1986,108(3):246-252.
    10. Gralnick HR, McKeown LP, Williams SB, et al. Plasma and platelet von Willebrand factor defects in uremia. Am J Med,1988,85(6):806-810.
    11. Zwaginga JJ, MJ IJ, de Groot PG, et al. Defects in platelet adhesion and aggregate formation in uremic bleeding disorder can be attributed to factors in plasma. Arterioscler Thromb,1991,11(3):733-744.
    12. Benigni A, Livio M, Dodesini P, et al. Inhibition of human platelet aggregation by parathyroid hormone. Is cyclic AMP implicated? Am J Nephrol,1985,5(4):243-247.
    13. Kyrle PA, Stockenhuber F, Brenner B, et al. Evidence for an increased generation of prostacyclin in the microvasculature and an impairment of the platelet alpha-granule release in chronic renal failure. Thromb Haemost,1988,60(2):205-208.
    14. Covic L, Gresser AL, Kuliopulos A. Biphasic kinetics of activation and signaling for PAR1 and PAR4 thrombin receptors in platelets. Biochemistry,2000,39(18):5458-5467.
    15. Shapiro MJ, Weiss EJ, Faruqi TR, et al. Protease-activated receptors 1 and 4 are shut off with distinct kinetics after activation by thrombin. J Biol Chem,2000, 275(33):25216-21.
    16. Diaz-Ricart M, Estebanell E, Cases A, et al. Abnormal platelet cytoskeletal assembly in hemodialyzed patients results in deficient tyrosine phosphorylation signaling. Kidney Int, 2000,57(5):1905-1914.
    17. Yang HX, Jiang HB. Clinical observation of combination of danshen and chuanxiongqin injection and astragali injection in patients with stable angina pectoris. J. Beth. Military Med,2008,3.
    18. Li S, Wan L. Experimental study on the preventive mechanism of salviae miltiorrhizae against atherosclerosis in rabbits models. J Huazhong Univ Sci Technolog Med Sci, 2004,24(3):233-235.
    19王艳,李岩。丹参川芎嗪注射液治疗缺血性结肠炎的疗效观察。胃肠病学和肝病学 杂志,2009,18(07):646-648
    20. Che XW, Zhang Y, Wang H, et al. Effect of ligustrazine injection on levels of interleukin-4 and interferon-gamma in patients with bronchial asthma. Chin J Integr Med, 2008,14(3):217-220.
    21. Li Y, Shen L,Chen R,et al. Effects of Salvia Miltiorrhiza Liguspyragine Hydrochlorid and Glucose Injection on the levels of main platelet thrombin receptors in chronic haemodialysis patients.Chin J Integr Med,2011,17(8):625-630.
    1. Colman, R. W., Marder, V. J., Salzman, E. W. et al. In Hemostasis and Thrombosis (eds Colman, R. W., Marder, V. J., Salzman, E. W.& Hirsh, J.) Lippincott, Philadelphia,1994,4(2):3-18.
    2.. Esmon, C. T. Inflammation, sepsis, and coagulation. Haematologica,1999, 84:254-259.
    3.吴蓝鸥,沈志强,吴平,等。凝血酶、花生四烯酸及阿司匹林对中性粒细胞与血小板之间粘附的影响。中国病理生理杂志,2003,19(1):269-231.
    4. Osterud, B. Tissue factor expression by monocytes:regulation and pathophysiological roles. Blood Coag. Fibrin,1998,9(1):9-14
    5. Giesen, P. L. Blood-borne tissue factor:another view of thrombosis. Proc. Natl Acad. Sci,1999,96:2311-2315.
    6. Coughlin, S. R. Sol Sherry lecture in thrombosis:how thrombin'talks'to cells:molecular mechanisms and roles in vivo. Arterioscl. Thromb. Vasc. Biol,1998,18:514-518.
    7.韩悦,谢颖,张威,等。蛋白激酶C与钙离子在凝血酶受体活化过程中的作用。中华血液学杂志,2008,29(3):154-157.
    8. Bevilacqua, M. P.& Gimbrone, M. A. Jr Inducible endothelial functions in inflammation and coagulation. Semin. Thromb. Hemost,1987,13:425-433.
    9.韩悦,卢晓旭,戴兰,等。腺苷二磷酸酯凝血酶信号传递过程中的作用。中华医学杂志,2006,86(46):256-258.
    10. Stenberg, P. E., McEver, R. P., Shuman, M. A., et al. A platelet alpha-granule membrane protein (GMP-140) is expressed on the plasma membrane after activation. J. Cell Biol,1985,101,880-886.
    11.明声,姚其正。抗血小板药物研究进展。中国医药指南,2012,10(5):261-565.
    12. Henn, V. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature,1998,391:591-594.
    13. Hughes, P. E.& Pfaff, M. Integrin affinity modulation. Trends Cell Biol,1998,8:359-364.
    14. Sims, P. J., Wiedmer, T., Esmon, C. T., et al. J. Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. J. Biol. Chem,1989,264:17049-17057.
    15. Pasquet, A Nurden,阮长耿。凝血酶受体活化与血小板膜糖蛋白Ibα的异位分布机制。中国血液学杂志,2005,26(3):152-156.
    16. Hattori, R., Hamilton, K. K., Fugate, R. D., et al. Stimulated secretion of endothelial vWF is accompanied by rapid redistribution to the cell surface of the intracellular granule membrane protein GMP-140. J. Biol. Chem,1989, 264:7768-7771.
    17.胡红心,石文霞,王婷。组织因子(TF)和蛋白酶激活受体(PARs)在肿瘤细胞的表达及其作用。血栓与止血学,2008,14(2):53-59.
    18.熊京,刘建社,等。蛋白酶激活受体2在小鼠肾间质纤维化中的表达及其意义。中华肾脏病杂志,2004,20(6):434-437.
    19. Subramaniam, M. Defects in hemostasis in P-selectin-deficient mice. Blood,1996,87:1238-1242.
    20. Coughlin, S. R. How the protease thrombin talks to cells. Proc. Natl Acad, 1999,84:11023-11027.
    21.皮国良,王涛。蛋白酶活化受体-1在肿瘤中的研究进展。实用医学杂志,2008,24(4):499-501.
    22. Rasmussen, U. B. cDNA cloning and expression of a hamster alpha-thrombin receptor coupled to Ca2+mobilization. FEBS Lett,1991,288:123-128.
    23. Vu, T.-K. H., Hung, D. T., Wheaton, V. I., et al. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell,1991,64:1057-1068.
    24.李凯。蛋白酶活化受体-1与肿瘤。实用癌症杂志,2006,21(2):216-218.
    25. Brien, P. J. Thrombin responses in human endothelial cells. Contributions from receptors other than PAR1 include the transactivation of PAR2 by thrombin-cleaved PAR1. J. Biol. Chem,2000,275:13502-13509.
    26. Anmax Pasquet, Alan Nurden,阮长耿。蛋白酶激活受体1与4在血小板活化中的作用机制。中国实用血液学杂志,2003,11(5):495-498.
    27. Ishii, K., Hein, L., Kobilka, B., et al. Kinetics of thrombin receptor cleavage on intact cells. Relation to signaling. J. Biol. Chem,1993,268: 9780-9786.
    28. Brnatowicz, M. S Development of potent thrombin receptor antagonist peptides. J. Med. Chem,1996,39:4879-4887.
    29.阮长耿。血小板凝血酶受体。国外医学生理、病理科学与临床分册,2002;22(1):4-6.
    30. Cn, J., Ishii, M., Wang, L., et al. Thrombin receptor activation: confirmation of the intramolecular tethered liganding hypothesis and discovery of an alternative intermolecular liganding mode. J. Biol. Chem,1994, 269:16041-16045.
    31. Sihara, H. Protease-activated receptor 3 is a second thrombin receptor in humans. Nature,1997,386:502-506.
    32.王海燕。蛋白酶活化受体4的研究进展。血栓与止血学。2008;14(2):80-82.
    33. Ntedt, S., Emilsson, K., Wahlestedt, et al. Molecular cloning of a potential novel proteinase activated receptor. Proc. Natl Acad,1994, 91:9208-9212.
    34. Mino, M. Interactions of mast cell tryptase with thrombin receptors and PAR-2. J. Biol. Chem,1997,272:4043-4049.
    35.凝血酶受体PAR1与PAR4在血小板活化中的作用机制。毕业论文。2002.
    36. Selak, M. A., Chignard, M., Smith, J. B. Cathepsin G is a strong platelet agonist released by neutrophils. Biochem. J,1988,251:293-299.
    37. Sbrano, G. R. Cathepsin G activates protease-activated receptor-4 in human platelets. J. Biol. Chem,2000,275:6819-6823.
    38. Adrews, R. K. The glycoprotein Ib-IX-V complex in platelet adhesion and signaling. Thromb. Haemost,1999,82:357-364.
    39.顾小红,房殿春,陈东风。PARs对肝纤维化大鼠HSC活化和增值的调控作用。胃肠病学和肝病学杂志,2007,16(4):357-360.
    40. Anolly, T. M. Species variability in platelet and other cellular responsiveness to thrombin receptor-derived peptides. Thromb. Haemost,1994, 72:627-633.
    41.吴鹤,黄小义,丛玉玮,等。大鼠脑缺血再灌后凝血酶与PAR1的表达与意义。卒中与神经疾病,2009,16(1):20-25.
    42. Nolly, A. J., Ishihara, H., Kahn, M. L., et al. Role of the thrombin receptor in development and evidence for a second receptor. Nature,1996,381:516-519.
    43.邹志强,李涛,陈镇奇,等。凝血酶和PARs激动肽诱导单核细胞分泌IL-6作用的研究。临床输血与检验,2011,13(4):294-300.
    44. Sng, D. T., Wong, Y. H., Vu, T.-K. H., et al. The cloned platelet thrombin receptor couples to at least two distinct effectors to stimulate both phosphoinositide hydrolysis and inhibit adenylyl cyclase. J. Biol. Chem,1992,353:20831-20834.
    45. Cmerer, E., Huang, W., Coughlin, S. R. Tissue factor-and Factor X-dependent activation of PAR2 by Factor VIIa. Proc. Natl Acad.,2000,97: 5255-5260.