纳米二氧化硅颗粒对HL-7702细胞凋亡的影响
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摘要
纳米二氧化硅具有特殊的理化性质,被广泛应用于医药卫生、材料、催化剂及催化载体等领域。人体接触机会和时间日益增加,其安全性问题受到广泛关注。
本研究对纳米二氧化硅颗粒致人正常肝细胞系HL-7702细胞凋亡进行了探讨。以人正常肝细胞系HL-7702为模型,研究不同浓度(25、50、100、200μg/mL)的纳米二氧化硅颗粒(60 nm)致HL-7702细胞凋亡。利用倒置生物显微镜观察细胞生长情况;采用HE染色法观察细胞形态变化;吉姆萨(Giemsa)染色法及流式细胞术(FCM)观察纳米二氧化硅对细胞凋亡的影响;罗丹明123(Rhodamin-123,Rh-123)标记FCM检测纳米二氧化硅对线粒体膜电位的影响;免疫细胞化学方法观察凋亡相关蛋白的表达情况。结果显示:HL-7702细胞形态改变;纳米二氧化硅颗粒(25、50、100、200μg/mL),可诱导HL-7702细胞凋亡,作用显著(P<0.01);纳米二氧化硅颗粒(25、50、100、200μg/mL)可引起线粒体膜电位下降,与对照组比较,有显著性差异(P<0.01);纳米二氧化硅颗粒(25、50、100、200μg/mL)可诱导Bcl-2、Bax、Cyt C及Caspase-3表达,与对照组比较,有显著性差异(P<0.01)。结论:不同浓度(25、50、100、200μg/mL)的纳米二氧化硅颗粒(60 nm),可引起HL-7702细胞形态改变,诱导凋亡,其诱导HL-7702细胞凋亡的作用机制可能是通过线粒体途径。
本研究为了解纳米二氧化硅的肝毒性,评价纳米二氧化硅的生物安全性提供实验依据。
In this study, human hepatic cell line HL-7702 was used as model to detect cell apoptosis after exposure to silica nanoparticles. Morphological changes in HL-7702 cells were observed under light microscopy after Haematoxylin and Eosin (HE) staining, cells apoptosis was detected by both Giemsa staining and flow cytometry (FCM) with AnnexinV-EGFP/PI double staining; mitochondrial membrane potential was examined by FCM with Rh-123 staining; and the expression of apoptosis related proteins were detected by immunocytochemical method. The results were shown as follow:
1. Morphological changes in HL-7702 cells induced by silica nanoparticles
In negative control group, HL-7702 cells were mostly polygonal with little particles in cytoplasm; in exposure groups, cell shape changed from polygonal to spindle length, cell number significantly decrease, more particulate matter were observed resulting in cell transparency decrease.
HE staining showed that after HL-7702 cells were treated with 25、50、100 and 200μg/mL of silica nanoparticles, cells exhibit morphological changes: cell number reduced, cell turning shrink, vacuolar degeneration in cytoplasm and nucleus increased,and trachychromatic chromatin and chromatin margination could also be observed.
2. Apoptosis in HL-7702 cells induced by silica nanoparticles
After HL-7702 cells were treated with 25、50、100 and 200μg/mL of silica nanoparticles, cell apoptosis were observed by light microscopy after Giemsa staining. The results showed silica nanoparticles could induce typical apoptotic changes: blebbing and chromatin condensation. Statistical analysis showed that the percentage of apoptotic cells was increased significantly at all exposed groups compared with control group (P<0.01).
FCM with AnnexinV-EGFP/PI double staining was also applied to detected apoptosis in HL7702 cells. After exposure to silica nanoparticles (25、50、100 and 200μg/mL) for 24 h, apoptotic rate significantly increased compared with control group (P<0.01). Although apoptotic rate continuously increased till at 100μg/mL silica treated group, it decreased at 200μg/mL group.
3. Changes of mitochondrial membrane potential in HL-7702 induced by silica nanoparticles
FCM with Rh-123 staining was used to detect the changes of mitochondrial membrane potential in HL7702 cells. After exposure to silica nanoparticles (25、50、100 and 200μg/mL) for 24 h, mitochondrial membrane potential decrease with the increasing dose, and there were significant differences between exposure and negative control group (P<0.01).
4. Expression of apoptosis related proteins in HL-7702 induced by silica nanoparticles
4.1 Expression of Bax、Bcl-2
After exposure to silica nanoparticles (25、50、100 and 200μg/mL) for 24 h, the expression of Bax、Bcl-2 enhanced with the increase of silica nanoparticles, there were significant differences between exposure and negative control group(P<0.01), and a decrease in Bcl-2/Bax ratio were also confirmed.
4.2 Expression of Cyt C、Caspase-3
After exposure to silica nanoparticles (25、50、100 and 200μg/mL) for 24 h, the expressions of Cyt C and Caspase-3 enhanced with the increase of silica nanoparticles, and there were significant differences in Cyt C、Caspase-3 expression between exposure and negative control group(P<0.01).
本研究对纳米二氧化硅颗粒致人正常肝细胞系HL-7702细胞凋亡进行了探讨。以人正常肝细胞系HL-7702为模型,研究不同浓度(25、50、100、200μg/mL)的纳米二氧化硅颗粒(60 nm)致HL-7702细胞凋亡。利用倒置生物显微镜观察细胞生长情况;采用HE染色法观察细胞形态变化;吉姆萨(Giemsa)染色法及流式细胞术(FCM)观察纳米二氧化硅对细胞凋亡的影响;罗丹明123(Rhodamin-123,Rh-123)标记FCM检测纳米二氧化硅对线粒体膜电位的影响;免疫细胞化学方法观察凋亡相关蛋白的表达情况。结果显示:HL-7702细胞形态改变;纳米二氧化硅颗粒(25、50、100、200μg/mL),可诱导HL-7702细胞凋亡,作用显著(P<0.01);纳米二氧化硅颗粒(25、50、100、200μg/mL)可引起线粒体膜电位下降,与对照组比较,有显著性差异(P<0.01);纳米二氧化硅颗粒(25、50、100、200μg/mL)可诱导Bcl-2、Bax、Cyt C及Caspase-3表达,与对照组比较,有显著性差异(P<0.01)。结论:不同浓度(25、50、100、200μg/mL)的纳米二氧化硅颗粒(60 nm),可引起HL-7702细胞形态改变,诱导凋亡,其诱导HL-7702细胞凋亡的作用机制可能是通过线粒体途径。
本研究为了解纳米二氧化硅的肝毒性,评价纳米二氧化硅的生物安全性提供实验依据。
In this study, human hepatic cell line HL-7702 was used as model to detect cell apoptosis after exposure to silica nanoparticles. Morphological changes in HL-7702 cells were observed under light microscopy after Haematoxylin and Eosin (HE) staining, cells apoptosis was detected by both Giemsa staining and flow cytometry (FCM) with AnnexinV-EGFP/PI double staining; mitochondrial membrane potential was examined by FCM with Rh-123 staining; and the expression of apoptosis related proteins were detected by immunocytochemical method. The results were shown as follow:
1. Morphological changes in HL-7702 cells induced by silica nanoparticles
In negative control group, HL-7702 cells were mostly polygonal with little particles in cytoplasm; in exposure groups, cell shape changed from polygonal to spindle length, cell number significantly decrease, more particulate matter were observed resulting in cell transparency decrease.
HE staining showed that after HL-7702 cells were treated with 25、50、100 and 200μg/mL of silica nanoparticles, cells exhibit morphological changes: cell number reduced, cell turning shrink, vacuolar degeneration in cytoplasm and nucleus increased,and trachychromatic chromatin and chromatin margination could also be observed.
2. Apoptosis in HL-7702 cells induced by silica nanoparticles
After HL-7702 cells were treated with 25、50、100 and 200μg/mL of silica nanoparticles, cell apoptosis were observed by light microscopy after Giemsa staining. The results showed silica nanoparticles could induce typical apoptotic changes: blebbing and chromatin condensation. Statistical analysis showed that the percentage of apoptotic cells was increased significantly at all exposed groups compared with control group (P<0.01).
FCM with AnnexinV-EGFP/PI double staining was also applied to detected apoptosis in HL7702 cells. After exposure to silica nanoparticles (25、50、100 and 200μg/mL) for 24 h, apoptotic rate significantly increased compared with control group (P<0.01). Although apoptotic rate continuously increased till at 100μg/mL silica treated group, it decreased at 200μg/mL group.
3. Changes of mitochondrial membrane potential in HL-7702 induced by silica nanoparticles
FCM with Rh-123 staining was used to detect the changes of mitochondrial membrane potential in HL7702 cells. After exposure to silica nanoparticles (25、50、100 and 200μg/mL) for 24 h, mitochondrial membrane potential decrease with the increasing dose, and there were significant differences between exposure and negative control group (P<0.01).
4. Expression of apoptosis related proteins in HL-7702 induced by silica nanoparticles
4.1 Expression of Bax、Bcl-2
After exposure to silica nanoparticles (25、50、100 and 200μg/mL) for 24 h, the expression of Bax、Bcl-2 enhanced with the increase of silica nanoparticles, there were significant differences between exposure and negative control group(P<0.01), and a decrease in Bcl-2/Bax ratio were also confirmed.
4.2 Expression of Cyt C、Caspase-3
After exposure to silica nanoparticles (25、50、100 and 200μg/mL) for 24 h, the expressions of Cyt C and Caspase-3 enhanced with the increase of silica nanoparticles, and there were significant differences in Cyt C、Caspase-3 expression between exposure and negative control group(P<0.01).
引文
[1] ROCO MC, BROADRE. Societal Issues of Nanotechnology [J]. J. Nanopart. Res., 2003, 5(3-4): 181-189.
[2] NNI (National Nanotechnology Initiative). What Is Nanotechnology (EB/OL). (2005-03-16). http://www.nano.gov/html/facts/what is nano.html.
[3] BIRRINGER R, GLETTER H, KLEIN HP. Classification of nanometer materials and basis [J]. Phys Lett., 1984, 102A: 365-369.
[4]陈友存.纳米化学发展现状[J].安庆师范院学报(自然科学版), 2002, 8(1): 65-69.
[5] ZHOU CAIMIN, YANG XIONGBO, XU RUIZHEN, et al. Present status and trends of nanomaterials [J]. Sci. Technol. Infor., 2008, (17): 17-18.
[6]张立德,牟季美.纳米材料与纳米结构[M].北京:科学出版社. 2001, 6.
[7] PROFFIT F. Nanotoxicology: Yellow light for nanotech [J]. Science, 2004, 305: 762.
[8] SERVICE RF. Nanotoxicology: Nanotoxicology grows up [J]. Science, 2004, 304: 1732 -1734.
[9]白春礼.纳米科技发展趋势分析[J].纳米科技, 2005, 5: 3-7.
[10]石士考.纳米材料的特性及其应用[J].大学化学, 2001, 16(2: 39-42.
[11] IWANAGA H, FUJII M. Inter-leg angles in tetrapod ZnO particles [J]. J. Cryst. Growth, 1998, 183(1-2): 190-195.
[12]徐辉碧.纳米医药[M].清华大学出版社, 2004, 12.
[13] MALIK MA, REVAPRASADU N, O'BRIEN P, et al. A novel route for the preparation of CuSe and CuInSe-nanoparticles [J]. Adv. Mater, 1999, 11(17): 1441-1444.
[14] LEGGET AJ, CHAKRAVARTY S, DORSEY AT, et al. Dynamic of the Disspative Two-State System [J]. Rev. Modphys, 1987, 59: 1-4.
[15] MASCIANGIOLI TM, ZHANG WX. Environmental technologies at the nanoscale: Potential&pitfalls [J]. Environ. Sci. Technol., 2003, 37: 102A-108A.
[16] RICE RF. Nanomaterials signs of toxicity [J]. Science, 300:243.
[17] GEOFF B. A little known knowledge [J]. Nature, 2424: 246.
[18]赵宇亮,柴之芳.纳米生物效应研究进展[J].中国科学院院刊, 2005, 20(3): 194-199.
[19] JENQ-SHENG ChANG, KE LIANG B ChANG, DENG-FWU HWANG, et al. In Vitro Cytotoxicitiy of Silica Nanoparticles at High Concentrations Strongly Depends on the Metabolic Activity Type of the Cell Line [J]. Environ. Sci. Technol., 2007, 41: 2064-2068.
[20] LAMCW, JAMES JT, MCCLUSKEY R, et al. A review of carbon nanotube toxicity and assessment of potential occupational and environmental health risks [J]. Crit. Rev. Toxicol., 2006, 36: 189-217.
[21] ZHANG Q, KUSAKA Y, ZHU X, et al. Comparative toxicity of standard nickel and ultrafinenickel in lung after intratracheal instillation [J]. J. Occup. Health, 2003, 45: 23-30.
[22]应杏秋,朱心强.超微颗粒毒性研究进展[J].国外医学卫生学分, 2005, 32(l): 6-10.
[23] LI XY, GLMOUR PS, DONALDSON K, MACNEE W. Free radical activity and Prochflamnatory effects of particulate air pollution(pMlo)in vivo and in vitro [J]. Thorax, 1996, 51: 1216-1222.
[24] MERMELSTEIN R, KILPPER RW, MORROW PE, et al. Lung overload: dosimetry of lung fibrosis and their implications to the respiratory-dust stardard [J]. Ann. Occup. Hyg., 1994, 38(11): 313–322.
[25] OBERDORSTER G. Lun Particle overload: implications for occupational exposures to particles [J]. Regult. Oxicol. Pharmacol, 1995, 21: 123-135.
[26] GURR JR, WANG AS, CHEN CH, et al. Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells [J]. Toxicology, 2005, 213(1-2): 66-73.
[27] BRAYDICH-STOLLE L, HUSSAIN S, SCHLAGER JJ, et al. In vitro cytotoxicity of nanoparticles in mammalian mammalian stem cells [J]. Toxicol. Sci., 2005, 88(2): 412-419.
[28] HUSSAIN SM, HESS KL, GEARHART JM, et al. In vitro toxicity of nanoparticles in BRL 3A rat liver cells [J]. Toxicol. In Vitro., 2005, 19(7): 975-983.
[29] DING LH, STILWELL J, ZHANG TT, et al. Molecular Characterization of the Cytotoxic Mechanism of Multiwall Carbon Nanotubes and Nano-Onions on Human Skin Fibroblast [J]. Nano. Lett., 2005, 5(12): 2448-2464.
[30] SCHUBERT D, DARGUSCH R, RAITANO J, et al. Cerium and yttrium oxide Nanoparticles are neuroprotective [J]. Biochem. Biophys. Res. Commun., 2006, 342: 86-91.
[31] BENNUDEZ E, MANGUM J B, WONG BA, et al. Pulmonary responses of mice,rats,and hamsters to subechronie inhalation of ultrafine titanium dioxide particles [J]. Toxicol.Sci., 2004, 77(2): 347-57.
[32] LAM CW, JANES JT, MECLUSKEY R, et al. Pulmonary toxicity of single-wall Carbon Nanotubes in mice 7 and 90 days after intratracheal instillation [J]. Toxicol. Sci., 2004, 77: 126- 134.
[33] WANG H, DENG J, DENG X, et al. Biodistribution of crbon single-wall Carbon Nanotubes in mice [J]. J. Nanosci. Nanotechnol, 2004, 4(8): 1019-1024.
[34]刘岚,唐萌,刘璐,等. FeZO3-Glu纳米颗粒在小鼠体内的代谢动力学研究[J].环境与职业医学, 2006, 23(1): l-3.
[35] YULIANG ZHAO, GENGMEI XING, ZHIFANG CHAI, Nanotoxicology: Are carbon nanotubes safe? [J]. Nature Nanotechnology, 2008, 3: 191-192.
[36] RENWICK LC, BROWN D, CLOUTER A, et al. Increased inflammation and inflammation and altered macro phage chemotactic responses caused by two ultrafineparticle types [J]. Occup. Environ. Med., 2004, 61: 442 -447
[37] BERRY CC, WELLS S, CHARLES S, et al. Cell response to dextran–derivatised iron oxide nano- particles post internalization [J]. Biomaterials, 2004, 25(23): 5405-5413.
[38] BERRY CC, WELLS S, CHARLES S, et al. Dextran and albumin derivatised iron oxide nanoparticles: influence on fibroblasts in vitro [J]. Biomaterials, 2003, 4(25): 4551-4557.
[39] HILGER I, FRUHAUF S, LINSS W, et al. Cytotoxicity of selected magnetic fluids on human adenocarcinoma cells [J]. Magn. Magn. Mater., 2003, 261(1-2): 7-12.
[40] GUPTA AK, GUPTA M. Cytotoxicity suppression and cellular uptake enhancement of surface modified magnetic nanoparticles [J]. Biomaterials, 2005, 26(13): 1565-1573.
[41] BRUNNE TJ, WICK P, MANSER P, et al. In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos,silica,and the effect of particle solubility [J]. Environ. Sci. Technol, 2006, 40(14): 4374-4381.
[42] NASTASSJA LEWINSKI, VICKI COLVIN , REBEKAH DREZEK. Cytotoxicity of Nanoparticles [J]. Small, 2008, 4(1): 26-49.
[43]李倩,唐萌,班婷婷,等.不同粒径纳米Fe2O3的细胞毒性及氧化作用[J].中国公共卫生, 2005, 21(5): 589-592.
[44] R SINGH, D PANATAROTTO, D MCCARTHY O, et al. Binding and condenstation of plasmid DNA onto functionalized carbon nanotubes: toward the construction of nanotube-based gene delivery vectors [J]. Am. Chem. Soc., 2005, 127: 4388-4396.
[45] Y PAN, A LEIFERT, W JAHNEN-DECHENT, et al. Size-dependent cytotoxicity of gold nanoparticles [J]. Small, 2007, 3: 1941-1949.
[46]毛彩霞,田熙科,杨光涛,等.纳米MnO2与常规MnO2粉末对Hela细胞DNA损伤的对比研究[J].生态毒理学报, 2007, 2(2): 191-194.
[47]中国科学院国家科学图书馆武汉分馆科学研究动态监测快报[R].生物安全专辑, 2007.
[48] WANG JJ, SANDERSON BJ, WANG H, et al. Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human lymphoblastoid cells [J]. Mutat. Res., 2007, 628: 99-106. [49 PV ASHARANI, GRACE.LOW.KAH.MUN, MANOOR.PRAKASH.HANDE. et al. Cytotoxicity and geno- toxicity of Silver Nanoparticles in Human Cells [J]. ACS Nano., 2009, 3(2): 279-290.
[50]王亚强,李玉平,郑廷秀,等.超细二氧化硅改性及其在建筑涂料中的应用[J].非金属矿, 2004, 27(3): 18-19.
[51]石璞,晋刚,瞿金平,等.纳米SiO2增强增韧聚丙烯的研究[J].中国塑料, 2002, 1: 27-31.
[52]葛雄章,李世荣,左美祥,等.纳米SiO2改性的彩色防水卷材[J].上海建材, 1998, 5: 21-24.
[53]吴春蕾,段先健,杨本意,等.高分散的气相法二氧化硅在医学领域的应用[R].有机硅氟咨讯, 2002, 12: 45-49.
[54] CULLUM BM, GRIFFIN GD, MILLER GH, et al. Intracellular meseurements in mammary carcinoma cells using fiber-optic nanosensors [J]. Anal. Biochem., 2000, 277: 25-32.
[55]陈春华,魏丽乔.医用导尿管的表面抗菌改性研究[J].第六届中国功能材料及其应用学术会议论文集, 2007: 1826-1827.
[56] BUI JD, ZELLES T, LOU HJ, et al. Probing intracellular dynamics with near-field optics [J]. J. Neuro- sci. Methods., 1999, 89: 9-15.
[57] VO-DINH T, CULLUM BM. Biosensors and biochips:advances in biological and medical diagnos- tics. Trese-nius [J]. J. Anal. Chem., 2000, 366: 540-541.
[58] VO-DINH T, ALARIE JP, CULLAM B, et al. Antibody based nanoro be for measurement of a fluores- cent analyte in a single cell [J]. Nat. Biotechmol., 2000, 18: 764-767.
[59] STOCKLE R, FOKAS L, DECKERT V, et al. High-qualiy near-field optical probes by tube etching [J]. Appl. Phys. Lett., 1999, 75: 160-162.
[60]卫星.功能纳米材料研究的新进展[J].上海金属, 2005, 27.
[61] JASON EF, GREGORY TZ, LINO SF, et al. Intracellular delivery of core-shell fluorescent silica nanoparticles. Biomaterials [J], Biomaterials, 2008, (29): 1526-1532
[62] KIM JS, YOON TJ, KIM HW, et al. Toxicity and Tissue Distribution of Magnetic Nanoparticles in Mice [J]. Toxicol, Sci. 2006, 89(1): 338-347.
[63] CHEN Y, CHEN J, DONG J, et al. Comparing study of the effect of nanosized silicon Dioxide and microsized silicon dioxide on fibrogenesis in rats [J]. Toxicol. Ind. Health, 2004, 20(l5): 21-27.
[64]应杏秋,曾群力,朱心强,等.纳米SiO2与标准SiO2致大鼠急性肺损伤的作用[J].中华劳动卫生职业病杂志, 2006, 24(2): 116-117.
[65]林本成,袭著革,杨丹凤,等.纳米级SiO2对雄性大鼠睾丸组织的氧化损伤作用[J].环境与健康杂志, 2007, 24(8): 574-576.
[66]金一和,赵翠霞,张颖花,等.纳米级与微米级二氧化硅粉尘对小鼠胚胎毒性的比较研究[J].卫生研究, 2007, 36(4): 414-416.
[67] HIKARU NISHIMORI, MASUO KONDOH, KIYOHITO YAGI. Silica nanoparticles as hepatotoxicants [J]. Euro. J. Phar. Biophar., 2009, inpress.
[68] CHEN M, VON MIKECZ A. Formation of nucleoplasmic protein aggregates impairs nuclear func- tion in response to SiO2 nanopartiales [J]. Exp. Cell Res., 2005, 305: 51-62.
[69]肖琳,付聪,杨旭,等.纳米SiO2与常规SiO2颗粒对Hela细胞的细胞毒性作用[J].生态毒理学报, 2007, 2(4): 435-439.
[70] JJ WANG, H WANG, BJ.S.SANDERSON. Ultrafine quartz-induced damage in human lymp- hoblastoid cells in vitro using three genetic damage end-points [J]. Toxicol. Mech. Methods, 2007, 17: 223-232.
[71] LIN WS, HUANG YW, MA YF, et al. In vitro toxicity of silica nanoparticles in human lung cancer cells [J]. Toxicol. Appl. Pharmacol, 2006, 217: 252-259.
[72] CUI D, GAO H. Advance and prospect of bionanomaterials [J]. Biotechnol. Porg., 2003, 19(3): 683-692.
[73]凌贻萍.细胞生物学[M].北京人民教育出版社, 2001: 235.
[74] ASSUNCAO GUIMARAES C, LINDEN R. Programmed cell deaths. Apoptosis and alternative death styles [J]. Eur. J. Biochem, 2004, 271(9): 1638-1650.
[75] VERMEULEN K, VAN BOCKSTAELE DR, BERNEMAN ZN, et al. Apoptosis: mechanisms and relevance in cancer [J]. Ann. Hematol, 2005, 84(10): 627-639.
[76] FULDA S, DEBATIN KM. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy [J]. Oncogene, 2006, 25(34): 4798-811.
[77]孔建强,赵琦.细胞凋亡机制的研究进展[J].生物技术通报, 2002, 3(1): 15-18.
[78]马丽焱.线粒体膜间隙蛋白在细胞凋亡中的作用[J].细胞生物学志, 2004, 26(1): 29-33.
[79] NEWMEYER DD, FERGUSON MILLER S. Mitochondria: Releasing power for life and unleashing ma- chineries of death [J]. Cell, 2003, 112(4): 481-490.
[80] GREEN DR, KROEMER G. The pathophysiology of mitochondrial cell death [J]. Science, 2004, 305(5684): 626-629.
[81]缪明永,王学敏,宋春桥,等.线粒体、细胞色素C与细胞凋亡[J].生命的化学, 1999, 19(2): 59-61.
[82] BRENNER C, CADIOU H, VIEIRA HL. et al. Bcl-2 and Bax regulate the channel activity of mitochon- drial adenine nucleotide translocator [J]. Oncogene, 2000, 19(3): 329-336.
[83]高晋华,王爱风.线粒体与细胞凋亡[J].山西教育学院学报, 1999, 2(4): 32-34.
[84]周祖平,刘树森. Bcl-2蛋白质家族——定位与转位[J].生物化学与生物物理紧张, 2001, 28(5): 650-653.
[85] LALIER L, CARTRON PF, JUIN P, et al. Bax activation andmitochondrial insertion during apoptosis [J]. Apoptosis, 2007, 12(5): 887-896.
[86] RAO RV, HERMEL E, CASTRO-OBREGON S, et al. Coupling endoplasmic reticulum stress to the cell death program: mechanism of Caspase activation [J]. J. Biol. Chem., 2001, 276(36): 33869-33874.
[87] SUSIN SA, LORENZO HZ, ZAMZAMI N, et al. Moleculs characterization of mitochon-drial apoptosis -inducing factor [J]. Nature, 1999, 97(6718): 441-445.
[88] HONARPOUR N, DU C, RICHARDSON JA, et al. Adult Apaf-1-deficient mice exhibit male infertility [J]. Dev. Biol., 2000, 218(2): 248-258.
[89]李嘉琦,吴娟. Caspase与细胞凋亡[J].动物医学进展, 2003, 2(1): 53-55.
[90]方敏,王晓东.细胞凋亡的线粒体通路[J].北京大学学报(医学版), 2002, 34(1): 1-10.
[91] JS KIM, TJ YOON, SJ PARK, et al. Toxicity and tissue distribution of magnetic nano- particles in mice [J]. Toxicol. Sci., 2006, 89: 338-347.
[92] BOTTINI M, ANNIBALE FD, MAGRINI A, et al. Quantum dot-doped silica nanoparticles as probes for targeting of T-lymphocytes [J]. Int. J. Nanomed, 2007, 2: 227-233.
[93] ZHANG FF, WAN Q, WANG XL, et al. Simultaneous assay of glucose, lactate, L-glutamate andhypoxanthine levels in a rat striatum using enzyme electrodes based on neutral red-doped silica nanoparticles [J]. Anal. Bioanal. Chem., 2004. 380: 637-642.
[94]杨菊云,张阳德,陈玉祥,等.硅纳米颗粒的体内分布及毒性试验[J].中国医学工程, 2005, 13(6): 585-590.
[95]杨辉,杨丹凤,袭著革,等. 4种典型纳米材料对小鼠胚胎成纤维细胞毒性的初步研究[J].生态毒理学, 2007, 2(4): 428-434.
[96] NEL A, XIA T, LI NING, et al. Toxic potential of materials at the nanolevel [J]. Science. 2006, 311: 622-627.
[97] KIPEN HM, LASKIN DL. Smaller is not always better : nanotechnology yields nanotoxi- cology [J]. Am. J. Physiol. Lung Cell Mol. Physiol., 2005, 289: 696-697.
[98] RYMAN-RASMUSSEN JP, RIVIERE JE, Monteiro-Riviere NA. Surface coatings determine cytotoxicity and irritation potential of quantum dot nanoparticles in epidermal keratinocytes [J]. J. Invest. Dermatol., 2007, 127(1): 143-153.
[99]林英武.放射性纳米药物与前哨淋巴结活检[J].国外医学肿瘤学分册, 2002, 29(2): 105-107.
[100] WANG ZIYU, LU XINLI, YAN SHIYAN, et al. Prepara tion and eva lua tion of As2O3 nanoparticles for trea tment of human liver cancer cells in vitro [J]. J. Southeast University, 2005, 21(1): 58-62.
[101] GUPA AK, CURTIS AS. Surface modified superparamagnetic nanoparticles for drug delivery: Inter-action studies with human fibroblasts in culture [J]. Mater. Sci. Mater Med., 2004, 15 (4): 493-496.
[102] ZHANG Y, KOHLER N, ZHANG M. Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake [J]. Biomaterials, 2002, 23(7): 1553-1561.
[103]徐东菁,张稷,孙皎,等.羟基磷灰石纳米颗粒诱导巨噬细胞凋亡及其与HSP70相互关系的研究[J].功能材料, 2007, 9(38): 1533-1536.
[104]李俊峡,张卓立,张莉代,等.超顺磁性氧化铁纳米粒子标记成肌细胞及其对细胞活性的影响[J].河北医药, 2007, 29(2): 102-104.
[105] BEMARDI P, SCORRANO L, COLONNA R, et al. Mitochondria and cell death [J]. Eur. J. Biochem, 1999, 264 (3): 687-701.
[106]来茂德.凋亡与坏死及相关问题.浙江大学学报(医学版). 2001, 30(6): 245-247.
[107]郑听,肝细胞凋亡机制及调控因素的研究进展,国外医学生理、病理科学与临床分册. 2000, 20(l): 22-25.
[108]周永烈,吕亚萍,邱莲女,等.硝普钠诱导K562细胞凋亡机制的研究[J].中国实验血液学杂志, 2005, 13(6): 983-988.
[109] PUCCI B, ADAMS CS, FERTALA J, et al. Development of the terminally differentiated statesensitizes epiphyseal chondrocytes to apoptosis through caspase-3 activation [J]. J. Cell Physiol, 2007, 210(3): 609-615.
[110] ADRAIN C, MARTIN SJ. The mitochondrial apoptosome: a killer unleashed by the cytochrome seas [J]. Trends. Biochem. Sci., 2001, 26(6): 390-397.
[111]马伟科,张宏艳.线粒体细胞色素C与细胞凋亡[J].实用医学杂志, 2007, 23(23): 3786-3788.
[112] LUO X, BUDIHARDJO I, ZOU H, et al. Bid, a bcl-2 interacting protein, mediates Cytochrome C release from mitochondria in response to activation of cell surface death response [J]. Cell, 1998, 94: 481-490.
[113] VANDER HEIDEN MG, CHANDEL NS, WILLIAMSON EK, et al. Bcl-XL regulate the membrane potential and volume homeostasis of mitochondria [J]. Cell, 1997, 91: 627-637.
[2] NNI (National Nanotechnology Initiative). What Is Nanotechnology (EB/OL). (2005-03-16). http://www.nano.gov/html/facts/what is nano.html.
[3] BIRRINGER R, GLETTER H, KLEIN HP. Classification of nanometer materials and basis [J]. Phys Lett., 1984, 102A: 365-369.
[4]陈友存.纳米化学发展现状[J].安庆师范院学报(自然科学版), 2002, 8(1): 65-69.
[5] ZHOU CAIMIN, YANG XIONGBO, XU RUIZHEN, et al. Present status and trends of nanomaterials [J]. Sci. Technol. Infor., 2008, (17): 17-18.
[6]张立德,牟季美.纳米材料与纳米结构[M].北京:科学出版社. 2001, 6.
[7] PROFFIT F. Nanotoxicology: Yellow light for nanotech [J]. Science, 2004, 305: 762.
[8] SERVICE RF. Nanotoxicology: Nanotoxicology grows up [J]. Science, 2004, 304: 1732 -1734.
[9]白春礼.纳米科技发展趋势分析[J].纳米科技, 2005, 5: 3-7.
[10]石士考.纳米材料的特性及其应用[J].大学化学, 2001, 16(2: 39-42.
[11] IWANAGA H, FUJII M. Inter-leg angles in tetrapod ZnO particles [J]. J. Cryst. Growth, 1998, 183(1-2): 190-195.
[12]徐辉碧.纳米医药[M].清华大学出版社, 2004, 12.
[13] MALIK MA, REVAPRASADU N, O'BRIEN P, et al. A novel route for the preparation of CuSe and CuInSe-nanoparticles [J]. Adv. Mater, 1999, 11(17): 1441-1444.
[14] LEGGET AJ, CHAKRAVARTY S, DORSEY AT, et al. Dynamic of the Disspative Two-State System [J]. Rev. Modphys, 1987, 59: 1-4.
[15] MASCIANGIOLI TM, ZHANG WX. Environmental technologies at the nanoscale: Potential&pitfalls [J]. Environ. Sci. Technol., 2003, 37: 102A-108A.
[16] RICE RF. Nanomaterials signs of toxicity [J]. Science, 300:243.
[17] GEOFF B. A little known knowledge [J]. Nature, 2424: 246.
[18]赵宇亮,柴之芳.纳米生物效应研究进展[J].中国科学院院刊, 2005, 20(3): 194-199.
[19] JENQ-SHENG ChANG, KE LIANG B ChANG, DENG-FWU HWANG, et al. In Vitro Cytotoxicitiy of Silica Nanoparticles at High Concentrations Strongly Depends on the Metabolic Activity Type of the Cell Line [J]. Environ. Sci. Technol., 2007, 41: 2064-2068.
[20] LAMCW, JAMES JT, MCCLUSKEY R, et al. A review of carbon nanotube toxicity and assessment of potential occupational and environmental health risks [J]. Crit. Rev. Toxicol., 2006, 36: 189-217.
[21] ZHANG Q, KUSAKA Y, ZHU X, et al. Comparative toxicity of standard nickel and ultrafinenickel in lung after intratracheal instillation [J]. J. Occup. Health, 2003, 45: 23-30.
[22]应杏秋,朱心强.超微颗粒毒性研究进展[J].国外医学卫生学分, 2005, 32(l): 6-10.
[23] LI XY, GLMOUR PS, DONALDSON K, MACNEE W. Free radical activity and Prochflamnatory effects of particulate air pollution(pMlo)in vivo and in vitro [J]. Thorax, 1996, 51: 1216-1222.
[24] MERMELSTEIN R, KILPPER RW, MORROW PE, et al. Lung overload: dosimetry of lung fibrosis and their implications to the respiratory-dust stardard [J]. Ann. Occup. Hyg., 1994, 38(11): 313–322.
[25] OBERDORSTER G. Lun Particle overload: implications for occupational exposures to particles [J]. Regult. Oxicol. Pharmacol, 1995, 21: 123-135.
[26] GURR JR, WANG AS, CHEN CH, et al. Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells [J]. Toxicology, 2005, 213(1-2): 66-73.
[27] BRAYDICH-STOLLE L, HUSSAIN S, SCHLAGER JJ, et al. In vitro cytotoxicity of nanoparticles in mammalian mammalian stem cells [J]. Toxicol. Sci., 2005, 88(2): 412-419.
[28] HUSSAIN SM, HESS KL, GEARHART JM, et al. In vitro toxicity of nanoparticles in BRL 3A rat liver cells [J]. Toxicol. In Vitro., 2005, 19(7): 975-983.
[29] DING LH, STILWELL J, ZHANG TT, et al. Molecular Characterization of the Cytotoxic Mechanism of Multiwall Carbon Nanotubes and Nano-Onions on Human Skin Fibroblast [J]. Nano. Lett., 2005, 5(12): 2448-2464.
[30] SCHUBERT D, DARGUSCH R, RAITANO J, et al. Cerium and yttrium oxide Nanoparticles are neuroprotective [J]. Biochem. Biophys. Res. Commun., 2006, 342: 86-91.
[31] BENNUDEZ E, MANGUM J B, WONG BA, et al. Pulmonary responses of mice,rats,and hamsters to subechronie inhalation of ultrafine titanium dioxide particles [J]. Toxicol.Sci., 2004, 77(2): 347-57.
[32] LAM CW, JANES JT, MECLUSKEY R, et al. Pulmonary toxicity of single-wall Carbon Nanotubes in mice 7 and 90 days after intratracheal instillation [J]. Toxicol. Sci., 2004, 77: 126- 134.
[33] WANG H, DENG J, DENG X, et al. Biodistribution of crbon single-wall Carbon Nanotubes in mice [J]. J. Nanosci. Nanotechnol, 2004, 4(8): 1019-1024.
[34]刘岚,唐萌,刘璐,等. FeZO3-Glu纳米颗粒在小鼠体内的代谢动力学研究[J].环境与职业医学, 2006, 23(1): l-3.
[35] YULIANG ZHAO, GENGMEI XING, ZHIFANG CHAI, Nanotoxicology: Are carbon nanotubes safe? [J]. Nature Nanotechnology, 2008, 3: 191-192.
[36] RENWICK LC, BROWN D, CLOUTER A, et al. Increased inflammation and inflammation and altered macro phage chemotactic responses caused by two ultrafineparticle types [J]. Occup. Environ. Med., 2004, 61: 442 -447
[37] BERRY CC, WELLS S, CHARLES S, et al. Cell response to dextran–derivatised iron oxide nano- particles post internalization [J]. Biomaterials, 2004, 25(23): 5405-5413.
[38] BERRY CC, WELLS S, CHARLES S, et al. Dextran and albumin derivatised iron oxide nanoparticles: influence on fibroblasts in vitro [J]. Biomaterials, 2003, 4(25): 4551-4557.
[39] HILGER I, FRUHAUF S, LINSS W, et al. Cytotoxicity of selected magnetic fluids on human adenocarcinoma cells [J]. Magn. Magn. Mater., 2003, 261(1-2): 7-12.
[40] GUPTA AK, GUPTA M. Cytotoxicity suppression and cellular uptake enhancement of surface modified magnetic nanoparticles [J]. Biomaterials, 2005, 26(13): 1565-1573.
[41] BRUNNE TJ, WICK P, MANSER P, et al. In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos,silica,and the effect of particle solubility [J]. Environ. Sci. Technol, 2006, 40(14): 4374-4381.
[42] NASTASSJA LEWINSKI, VICKI COLVIN , REBEKAH DREZEK. Cytotoxicity of Nanoparticles [J]. Small, 2008, 4(1): 26-49.
[43]李倩,唐萌,班婷婷,等.不同粒径纳米Fe2O3的细胞毒性及氧化作用[J].中国公共卫生, 2005, 21(5): 589-592.
[44] R SINGH, D PANATAROTTO, D MCCARTHY O, et al. Binding and condenstation of plasmid DNA onto functionalized carbon nanotubes: toward the construction of nanotube-based gene delivery vectors [J]. Am. Chem. Soc., 2005, 127: 4388-4396.
[45] Y PAN, A LEIFERT, W JAHNEN-DECHENT, et al. Size-dependent cytotoxicity of gold nanoparticles [J]. Small, 2007, 3: 1941-1949.
[46]毛彩霞,田熙科,杨光涛,等.纳米MnO2与常规MnO2粉末对Hela细胞DNA损伤的对比研究[J].生态毒理学报, 2007, 2(2): 191-194.
[47]中国科学院国家科学图书馆武汉分馆科学研究动态监测快报[R].生物安全专辑, 2007.
[48] WANG JJ, SANDERSON BJ, WANG H, et al. Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human lymphoblastoid cells [J]. Mutat. Res., 2007, 628: 99-106. [49 PV ASHARANI, GRACE.LOW.KAH.MUN, MANOOR.PRAKASH.HANDE. et al. Cytotoxicity and geno- toxicity of Silver Nanoparticles in Human Cells [J]. ACS Nano., 2009, 3(2): 279-290.
[50]王亚强,李玉平,郑廷秀,等.超细二氧化硅改性及其在建筑涂料中的应用[J].非金属矿, 2004, 27(3): 18-19.
[51]石璞,晋刚,瞿金平,等.纳米SiO2增强增韧聚丙烯的研究[J].中国塑料, 2002, 1: 27-31.
[52]葛雄章,李世荣,左美祥,等.纳米SiO2改性的彩色防水卷材[J].上海建材, 1998, 5: 21-24.
[53]吴春蕾,段先健,杨本意,等.高分散的气相法二氧化硅在医学领域的应用[R].有机硅氟咨讯, 2002, 12: 45-49.
[54] CULLUM BM, GRIFFIN GD, MILLER GH, et al. Intracellular meseurements in mammary carcinoma cells using fiber-optic nanosensors [J]. Anal. Biochem., 2000, 277: 25-32.
[55]陈春华,魏丽乔.医用导尿管的表面抗菌改性研究[J].第六届中国功能材料及其应用学术会议论文集, 2007: 1826-1827.
[56] BUI JD, ZELLES T, LOU HJ, et al. Probing intracellular dynamics with near-field optics [J]. J. Neuro- sci. Methods., 1999, 89: 9-15.
[57] VO-DINH T, CULLUM BM. Biosensors and biochips:advances in biological and medical diagnos- tics. Trese-nius [J]. J. Anal. Chem., 2000, 366: 540-541.
[58] VO-DINH T, ALARIE JP, CULLAM B, et al. Antibody based nanoro be for measurement of a fluores- cent analyte in a single cell [J]. Nat. Biotechmol., 2000, 18: 764-767.
[59] STOCKLE R, FOKAS L, DECKERT V, et al. High-qualiy near-field optical probes by tube etching [J]. Appl. Phys. Lett., 1999, 75: 160-162.
[60]卫星.功能纳米材料研究的新进展[J].上海金属, 2005, 27.
[61] JASON EF, GREGORY TZ, LINO SF, et al. Intracellular delivery of core-shell fluorescent silica nanoparticles. Biomaterials [J], Biomaterials, 2008, (29): 1526-1532
[62] KIM JS, YOON TJ, KIM HW, et al. Toxicity and Tissue Distribution of Magnetic Nanoparticles in Mice [J]. Toxicol, Sci. 2006, 89(1): 338-347.
[63] CHEN Y, CHEN J, DONG J, et al. Comparing study of the effect of nanosized silicon Dioxide and microsized silicon dioxide on fibrogenesis in rats [J]. Toxicol. Ind. Health, 2004, 20(l5): 21-27.
[64]应杏秋,曾群力,朱心强,等.纳米SiO2与标准SiO2致大鼠急性肺损伤的作用[J].中华劳动卫生职业病杂志, 2006, 24(2): 116-117.
[65]林本成,袭著革,杨丹凤,等.纳米级SiO2对雄性大鼠睾丸组织的氧化损伤作用[J].环境与健康杂志, 2007, 24(8): 574-576.
[66]金一和,赵翠霞,张颖花,等.纳米级与微米级二氧化硅粉尘对小鼠胚胎毒性的比较研究[J].卫生研究, 2007, 36(4): 414-416.
[67] HIKARU NISHIMORI, MASUO KONDOH, KIYOHITO YAGI. Silica nanoparticles as hepatotoxicants [J]. Euro. J. Phar. Biophar., 2009, inpress.
[68] CHEN M, VON MIKECZ A. Formation of nucleoplasmic protein aggregates impairs nuclear func- tion in response to SiO2 nanopartiales [J]. Exp. Cell Res., 2005, 305: 51-62.
[69]肖琳,付聪,杨旭,等.纳米SiO2与常规SiO2颗粒对Hela细胞的细胞毒性作用[J].生态毒理学报, 2007, 2(4): 435-439.
[70] JJ WANG, H WANG, BJ.S.SANDERSON. Ultrafine quartz-induced damage in human lymp- hoblastoid cells in vitro using three genetic damage end-points [J]. Toxicol. Mech. Methods, 2007, 17: 223-232.
[71] LIN WS, HUANG YW, MA YF, et al. In vitro toxicity of silica nanoparticles in human lung cancer cells [J]. Toxicol. Appl. Pharmacol, 2006, 217: 252-259.
[72] CUI D, GAO H. Advance and prospect of bionanomaterials [J]. Biotechnol. Porg., 2003, 19(3): 683-692.
[73]凌贻萍.细胞生物学[M].北京人民教育出版社, 2001: 235.
[74] ASSUNCAO GUIMARAES C, LINDEN R. Programmed cell deaths. Apoptosis and alternative death styles [J]. Eur. J. Biochem, 2004, 271(9): 1638-1650.
[75] VERMEULEN K, VAN BOCKSTAELE DR, BERNEMAN ZN, et al. Apoptosis: mechanisms and relevance in cancer [J]. Ann. Hematol, 2005, 84(10): 627-639.
[76] FULDA S, DEBATIN KM. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy [J]. Oncogene, 2006, 25(34): 4798-811.
[77]孔建强,赵琦.细胞凋亡机制的研究进展[J].生物技术通报, 2002, 3(1): 15-18.
[78]马丽焱.线粒体膜间隙蛋白在细胞凋亡中的作用[J].细胞生物学志, 2004, 26(1): 29-33.
[79] NEWMEYER DD, FERGUSON MILLER S. Mitochondria: Releasing power for life and unleashing ma- chineries of death [J]. Cell, 2003, 112(4): 481-490.
[80] GREEN DR, KROEMER G. The pathophysiology of mitochondrial cell death [J]. Science, 2004, 305(5684): 626-629.
[81]缪明永,王学敏,宋春桥,等.线粒体、细胞色素C与细胞凋亡[J].生命的化学, 1999, 19(2): 59-61.
[82] BRENNER C, CADIOU H, VIEIRA HL. et al. Bcl-2 and Bax regulate the channel activity of mitochon- drial adenine nucleotide translocator [J]. Oncogene, 2000, 19(3): 329-336.
[83]高晋华,王爱风.线粒体与细胞凋亡[J].山西教育学院学报, 1999, 2(4): 32-34.
[84]周祖平,刘树森. Bcl-2蛋白质家族——定位与转位[J].生物化学与生物物理紧张, 2001, 28(5): 650-653.
[85] LALIER L, CARTRON PF, JUIN P, et al. Bax activation andmitochondrial insertion during apoptosis [J]. Apoptosis, 2007, 12(5): 887-896.
[86] RAO RV, HERMEL E, CASTRO-OBREGON S, et al. Coupling endoplasmic reticulum stress to the cell death program: mechanism of Caspase activation [J]. J. Biol. Chem., 2001, 276(36): 33869-33874.
[87] SUSIN SA, LORENZO HZ, ZAMZAMI N, et al. Moleculs characterization of mitochon-drial apoptosis -inducing factor [J]. Nature, 1999, 97(6718): 441-445.
[88] HONARPOUR N, DU C, RICHARDSON JA, et al. Adult Apaf-1-deficient mice exhibit male infertility [J]. Dev. Biol., 2000, 218(2): 248-258.
[89]李嘉琦,吴娟. Caspase与细胞凋亡[J].动物医学进展, 2003, 2(1): 53-55.
[90]方敏,王晓东.细胞凋亡的线粒体通路[J].北京大学学报(医学版), 2002, 34(1): 1-10.
[91] JS KIM, TJ YOON, SJ PARK, et al. Toxicity and tissue distribution of magnetic nano- particles in mice [J]. Toxicol. Sci., 2006, 89: 338-347.
[92] BOTTINI M, ANNIBALE FD, MAGRINI A, et al. Quantum dot-doped silica nanoparticles as probes for targeting of T-lymphocytes [J]. Int. J. Nanomed, 2007, 2: 227-233.
[93] ZHANG FF, WAN Q, WANG XL, et al. Simultaneous assay of glucose, lactate, L-glutamate andhypoxanthine levels in a rat striatum using enzyme electrodes based on neutral red-doped silica nanoparticles [J]. Anal. Bioanal. Chem., 2004. 380: 637-642.
[94]杨菊云,张阳德,陈玉祥,等.硅纳米颗粒的体内分布及毒性试验[J].中国医学工程, 2005, 13(6): 585-590.
[95]杨辉,杨丹凤,袭著革,等. 4种典型纳米材料对小鼠胚胎成纤维细胞毒性的初步研究[J].生态毒理学, 2007, 2(4): 428-434.
[96] NEL A, XIA T, LI NING, et al. Toxic potential of materials at the nanolevel [J]. Science. 2006, 311: 622-627.
[97] KIPEN HM, LASKIN DL. Smaller is not always better : nanotechnology yields nanotoxi- cology [J]. Am. J. Physiol. Lung Cell Mol. Physiol., 2005, 289: 696-697.
[98] RYMAN-RASMUSSEN JP, RIVIERE JE, Monteiro-Riviere NA. Surface coatings determine cytotoxicity and irritation potential of quantum dot nanoparticles in epidermal keratinocytes [J]. J. Invest. Dermatol., 2007, 127(1): 143-153.
[99]林英武.放射性纳米药物与前哨淋巴结活检[J].国外医学肿瘤学分册, 2002, 29(2): 105-107.
[100] WANG ZIYU, LU XINLI, YAN SHIYAN, et al. Prepara tion and eva lua tion of As2O3 nanoparticles for trea tment of human liver cancer cells in vitro [J]. J. Southeast University, 2005, 21(1): 58-62.
[101] GUPA AK, CURTIS AS. Surface modified superparamagnetic nanoparticles for drug delivery: Inter-action studies with human fibroblasts in culture [J]. Mater. Sci. Mater Med., 2004, 15 (4): 493-496.
[102] ZHANG Y, KOHLER N, ZHANG M. Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake [J]. Biomaterials, 2002, 23(7): 1553-1561.
[103]徐东菁,张稷,孙皎,等.羟基磷灰石纳米颗粒诱导巨噬细胞凋亡及其与HSP70相互关系的研究[J].功能材料, 2007, 9(38): 1533-1536.
[104]李俊峡,张卓立,张莉代,等.超顺磁性氧化铁纳米粒子标记成肌细胞及其对细胞活性的影响[J].河北医药, 2007, 29(2): 102-104.
[105] BEMARDI P, SCORRANO L, COLONNA R, et al. Mitochondria and cell death [J]. Eur. J. Biochem, 1999, 264 (3): 687-701.
[106]来茂德.凋亡与坏死及相关问题.浙江大学学报(医学版). 2001, 30(6): 245-247.
[107]郑听,肝细胞凋亡机制及调控因素的研究进展,国外医学生理、病理科学与临床分册. 2000, 20(l): 22-25.
[108]周永烈,吕亚萍,邱莲女,等.硝普钠诱导K562细胞凋亡机制的研究[J].中国实验血液学杂志, 2005, 13(6): 983-988.
[109] PUCCI B, ADAMS CS, FERTALA J, et al. Development of the terminally differentiated statesensitizes epiphyseal chondrocytes to apoptosis through caspase-3 activation [J]. J. Cell Physiol, 2007, 210(3): 609-615.
[110] ADRAIN C, MARTIN SJ. The mitochondrial apoptosome: a killer unleashed by the cytochrome seas [J]. Trends. Biochem. Sci., 2001, 26(6): 390-397.
[111]马伟科,张宏艳.线粒体细胞色素C与细胞凋亡[J].实用医学杂志, 2007, 23(23): 3786-3788.
[112] LUO X, BUDIHARDJO I, ZOU H, et al. Bid, a bcl-2 interacting protein, mediates Cytochrome C release from mitochondria in response to activation of cell surface death response [J]. Cell, 1998, 94: 481-490.
[113] VANDER HEIDEN MG, CHANDEL NS, WILLIAMSON EK, et al. Bcl-XL regulate the membrane potential and volume homeostasis of mitochondria [J]. Cell, 1997, 91: 627-637.