优可洛外用治疗尖锐湿疣的机理初探
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摘要
背景：
尖锐湿疣(CA)是一种常见的性传播疾病之一,近年来发病率不断上升,再加上其能诱发宫颈癌、鳞状上皮细胞癌等恶性肿瘤,故日益受到人们的重视。目前临床上治疗尖锐湿疣的中药外用药物很多,但大都作用机制不明。优可洛是我科近年来治疗尖锐湿疣使用的中药提取物外用药,疗效显著,本课题将从细胞生物学方面对优可洛的作用机制进行探讨。
方法：
采用免疫组化SP法检测优可治疗前后17例女性尖锐湿疣患者的皮损局部的Mcm2和Caspase-3的表达情况,并用TUNEL法检测治疗前后表皮细胞的凋亡情况。应用SPSS17.0统计软件分析。
结果：
17例女性尖锐湿疣患者治疗前局部皮损的细胞增殖指数为55.35±14.41,治疗后局部皮损的细胞增殖指数为16.06±14.10,差异有显著统计学意义(z=-3.623aP<0.01)；治疗前Caspase-3的表达为6.12±2.93,治疗后Caspase-3的表达为9.59±6.84,差异有显著统计学意义(t=2.368,P<0.05)；治疗前TUNEL检测的细胞凋亡指数为18.12±9.77,治疗后为27.82±15.19,差异有统计学意义(z=-1.967aP<0.05)。
结论：
优可洛的作用机制,可能是通过抑制表皮细胞增殖,促进细胞凋亡而发挥作用的。
Objective
Condyloma acuminatum(CA) is one of the common sexually transmitted disease in clinical, and there is a gradual upward trend recently, secondly it may cause cancer such as cervical cancer, Squamous cell carcinoma and so on, which led to a high degree of human attention. There are many traditional topical drugs which are used on treatment of Condyloma acuminatum in clinical,but the mechanism of them are usually unkonwn. If we kown the mechanism, it will be useful for the treatment of Condyloma acuminatum. This research is to study the possible mechanism of "youkeluo" in cell biology.
Method
The expression of Mcm2, Caspase-3of epidemic cells of17female cases of CA were detected by SP immunohistochemicel technique. Cell apoptosis index was determinated by TUNEL method. The softwareof spss17will be used to analysis the data.
Results
17female patients were treatd by youkeluo:the cell proliferating index labelig in Mcm2before treatment was55.35±14.41, and after treatment it was16.06±14.10, there was statistical significance(z=-3.623a, P<0.01); the expression of Caspase-3was6.12±2.93before treatment, and after treatment it was10.88±1.88, which was higher than that before, there was statistical signif icance(t=2.368, P<0.01); the cell apoptosis index laheling in TUNEL before treatment was18.12±9.77, and after treatment it was27.82±15.19, which was higher than that before, there was statistical significance (z=-1.967a, P<0.05).
Conclusion
The effectidve mechanism of youtuoxin may take effect through inlibiting cell proliferating and promote cell apoptosis.
尖锐湿疣(CA)是一种常见的性传播疾病之一,近年来发病率不断上升,再加上其能诱发宫颈癌、鳞状上皮细胞癌等恶性肿瘤,故日益受到人们的重视。目前临床上治疗尖锐湿疣的中药外用药物很多,但大都作用机制不明。优可洛是我科近年来治疗尖锐湿疣使用的中药提取物外用药,疗效显著,本课题将从细胞生物学方面对优可洛的作用机制进行探讨。
方法：
采用免疫组化SP法检测优可治疗前后17例女性尖锐湿疣患者的皮损局部的Mcm2和Caspase-3的表达情况,并用TUNEL法检测治疗前后表皮细胞的凋亡情况。应用SPSS17.0统计软件分析。
结果：
17例女性尖锐湿疣患者治疗前局部皮损的细胞增殖指数为55.35±14.41,治疗后局部皮损的细胞增殖指数为16.06±14.10,差异有显著统计学意义(z=-3.623aP<0.01)；治疗前Caspase-3的表达为6.12±2.93,治疗后Caspase-3的表达为9.59±6.84,差异有显著统计学意义(t=2.368,P<0.05)；治疗前TUNEL检测的细胞凋亡指数为18.12±9.77,治疗后为27.82±15.19,差异有统计学意义(z=-1.967aP<0.05)。
结论：
优可洛的作用机制,可能是通过抑制表皮细胞增殖,促进细胞凋亡而发挥作用的。
Objective
Condyloma acuminatum(CA) is one of the common sexually transmitted disease in clinical, and there is a gradual upward trend recently, secondly it may cause cancer such as cervical cancer, Squamous cell carcinoma and so on, which led to a high degree of human attention. There are many traditional topical drugs which are used on treatment of Condyloma acuminatum in clinical,but the mechanism of them are usually unkonwn. If we kown the mechanism, it will be useful for the treatment of Condyloma acuminatum. This research is to study the possible mechanism of "youkeluo" in cell biology.
Method
The expression of Mcm2, Caspase-3of epidemic cells of17female cases of CA were detected by SP immunohistochemicel technique. Cell apoptosis index was determinated by TUNEL method. The softwareof spss17will be used to analysis the data.
Results
17female patients were treatd by youkeluo:the cell proliferating index labelig in Mcm2before treatment was55.35±14.41, and after treatment it was16.06±14.10, there was statistical significance(z=-3.623a, P<0.01); the expression of Caspase-3was6.12±2.93before treatment, and after treatment it was10.88±1.88, which was higher than that before, there was statistical signif icance(t=2.368, P<0.01); the cell apoptosis index laheling in TUNEL before treatment was18.12±9.77, and after treatment it was27.82±15.19, which was higher than that before, there was statistical significance (z=-1.967a, P<0.05).
Conclusion
The effectidve mechanism of youtuoxin may take effect through inlibiting cell proliferating and promote cell apoptosis.
引文
[1]杨戈,林昭春等.3489例尖锐湿疣流行病学分析[J].中国性病艾滋病防治,2007,13(2)：143-145.
[2]周剑波等.人乳头瘤病毒检测及临床应用[J].职业与健康,2008,24(19)：2102-2104.
[3]练霭云.中医药学刊[J].尖锐湿疣发病机理的研究评述,2004,22(5)：895-896.
[4]廖元兴.尖锐湿疣与相似皮肤病的诊断与治疗[M].第一版.江西： 科学技术出版社.2004：159.(著作)
[5]龚向东,叶顺章,张国成等.2000年全国性病流行病学分析[J].中国性病艾滋病防治,2001,7(3)：131—134.
[6]陈志伟.皮肤性病辨治精要[M].北京：人民军医出版社.2007：78-79.(著作)
[7]Matlashewski G, Schneider J, Banks L, et al. Human papillo-mavirus type 16 DNA cooperates with activated ras in transforming primary cells[J]. EMBO J,2005,24(4): 1502-1507.
[8]Marshall K. Cervical dysplasia:early intervention. Alterm Med Rev.2003,8 (2): 156-170.
[9]Munoz N, Bosch FX, de-Sanjose S, et al. Epidemiologie classification of human papillomavirus types associated with cervical cancer. NEngl J Med,2003,348(6): 518-527.
[10]吴志华.现代性病学[M].广州：广东人民出版社.2002：193.
[11]韩国柱.尖锐湿疣研究进展[J].中国麻风皮肤病杂志,2002,18(4)：385-387.
[12]卢勇田.尖锐湿疣国内外诊断治疗的现状和进展[J].中国医学文摘-皮肤科学,2007,24(5)：273-276.
[13]王松挺.中国肛肠病杂志[J].尖锐湿疣的治疗进展,2007,27(9)：45-47
[14]应作霖,吴瑞勤.皮肤病与性病[J].尖锐湿疣患者的免疫功能和免疫治疗研究进展,2006,18(3)：12-15.
[15]Golsteln P.Controling cell death[J]. Science,1997,275(5303):1081-1082.
[16]李晓萍等.鸦胆子治疗尖锐湿疣24例[J].ACPM,2002,12(4)：54-55.
[17]王霄鹏.中国伤残医学[J].贯众散防治尖锐湿疣电灼后复发的临床观察,2008,16(4)：82-83
[18]王凝芳,陈菊梅.传染病学[M].第一版.北京：中国协和医科大学出版社,2000,257-261.(著作)
[19]Morelli AE, Belardi G, Dipaola G, et al. Cellular subsets and epithe - lial ICAM -1 and HLA —DR expression in human papillomavirus infection of the vulva[J]. Acta Derm Venereol.1994,74(1):45-50.
[20]Sheets EE, Yeh J. The role of apoptosis in gynaecological malignancies[J]. Ann Med,1997:29(2):121-126.
[21]Tjalma WA, WeylerJJ, Bogers JJ, et al. The importance of bioligical factors(bcl-2, bax, p53, PCNA, MI HPV and angiogenesis)in invasive crevical cancer[J]. Eur J Obstet Repord Biol,2001;97(2):223-230.
[22]侯孟君,范瑞强等.中药疣毒净对离体人乳头状瘤病毒DNA的影响[J].广州中医药大学学报,1998,15(1)：56-58.
[23]闻玉梅.现代医学微生物学[M].上海：上海医科大学出版社,1999,957-967.
[24]宋丽君等.国外医学妇幼保健杂志[J].尖锐湿疣的免疫学发病机制及免疫治疗进展,2003,14(4)：229-231.
[25]Coleman N, Birley HD, Renton AN, et al. Immunological events in re—gressing genital warts [J]. Am J Clin Pathol.1994,102(6):768-774.
[26]Huang GT, Zhang X, Park NH. Increased ICAM-1 expression in transformed human oral epithelial cells:molecular mechanism and func—tional role in peripheral blood mononuclear cell adhesion and lymphokine— activated—killer cell cytotoxicity[J]. InI J Oncol,2000,17(3):479—486.
[27]刘冬先等.中华皮肤科杂志[J].尖锐湿疣患者外周血CD8+T细胞细胞因子的表达,2007,40(11)：674-675.
[28]刘冬先等.中国皮肤性病学杂志[J].尖锐湿疣患者外周血 CD4+T细胞细胞因子的检测,2007,21(7)：414-415.
[29]马勇刘彤.细胞与分子生物学杂志[J].尖锐湿疣组织中IFN-γ mRNA和IL-4mRNA的表达,2008,24(4)：368-369.
[30]郭庆曾凡钦等.中华皮肤科杂志[J].尖锐湿疣皮损活化抗原CD69、CD38、HLA—DR的表达及其意义,2007,40(9)：543-545.
[31]林友胜,张玉梅.四川医学[J]. PCNA、p53、Ki-67在尖锐湿疣中的表达和意义,2007,28(3)：322-323.
[32]胡野凌志强单小云编著.细胞凋亡的分子医学[M].北京：军事医学科学出版社,2002：335.(著作)
[33]宋今丹等.医学细胞生物学[M].北京：人民卫生出版社,第三版,2004：259.(著作)
[34]劳山 陈罡等.微创医学[J].肿瘤细胞增殖标志物蛋白功能及意义的研究进展,2009,4(3)：273-275.
[35]Szajerka A. Dziegiel P. Szajerka T Immunohistochemical evaluation of metallothionein, Mcm-2 and Ki-67 antigen expression in tumors of the adrenal cortex[J]. Antlcancer Res.2008,28 (5B):2959-2965.
[36]Nishihara K. Shomori K. Fujioka S Minichromosome maintenance protein 7 in colorectalcaneer:impliCafion of prognostic significance[J]. Int J Oncol,2008,33(2): 245—251.
[37]Burger M. Denzinger S. Hartmann A Mcm2 predicts recurrence hazard in stage Ta/T1 bladder cancer more accurately than CK20, Ki67 and histological grade[J]. 2007,96(11):1711-1715.
[38]Ivan T. Tedorov, Brace A. Wemem. dal. HsMCM2/BM28:A novd pmlif erationnlarker for human tumoursand normal tissues.Laboratory Investigation,1998; 78:73—78.
[39]李斌等.中华临床新医学[J].MCM2蛋白表达研究的临床意义,2003,3(10)：907-908.
[40]Williams G H, Romanowski P, Morris L, et al. Improved cervical smear assessment using an tibodies against proteins that regulate DNA replication[J3. Proe Natl Acad Sci USA,1998,95(25):14932—14937.
[41]Freeman A, Morris L S, Mills A D, et al. Minichromosome maintenance proteins as biological markers of dysplasia and malignancy[J]. Clin Cancer Res,1999,5(8):2121—2132.
[42]李艳玲等.中国皮肤性病学杂志[J].尖锐湿疣和鲍温样丘疹病皮损中MCM一2蛋白的检测,2008,22(7)：398-400.
[43]易铁男等.国外医学肿瘤学分册[J]. Caspase家族与细胞凋亡的研究进展,2001,28(1)：39-42.
[44]戴听等.中国现代医药杂志[J].凋亡相关蛋白Caspase研究进展,2010,12(4)：130-132。
[45]祝兴旺,宋彦等.医学临床研究[J].凋亡相关蛋白Livin及Caspase — 3在膀胱移行细胞癌中的表达及临床意义,2008,25(11)：1955-1957.
[46]Takahashi T. Ogo M. Hibino T. Partial purification and characterization of two distinct types of caspases from human epidermis. J Invest Dennatol 1998:111:367—372.
[47]Eckhart L, Ban J, Fischer H, el al. Caspase— 14:analysis of gene structure and mRNA expression during keratinocyte diferentiation. Biochem Biophys Res Commun 2000:277:655—659.
[48]Lippens S, Kockx M, Knaapen M, et al. Epidermal diferentiation does not involve the pmapoptotic executioner caspases, but is associated wi th caspase — 14 induction and processing. Cell Death Diffter 2000; 7:1218 - 1224.
[49]Konstan ti—nidou AE, Givalos N, Gakiopo ulou H, et al. Caspa--3 immunohistochemical expresion is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas. Apoptosis 2006; 5:[Epub ahead of print].
[50]杨戈等.中国麻风皮肤病杂志[J].HPV载量、PCNA和Caspase — 3的表与尖锐湿疣发病相关 性研究进展,2007,23(11)：991-993.
[51]熊芬等.临床及实验研究[J].尖锐湿疣细胞凋亡与caspase - 3、bcl - 2的表达,2006,28(4)：4-6.
[52]尹光文等.中华皮肤科杂志[J].生存素mRNA和Caspase - 3在尖锐湿疣组织中的表达,2006,39(5)：292-293.
[53]魏国等.中国麻风皮肤病杂志[J].消疣煎外洗对CA患者皮损PCNA表达的影响.2006,22(2)：129-130.
[54]李英等.中国中西医结合皮肤性病学杂志[J].祛疣洗剂治疗尖锐湿疣的临床研究及其作用机制,2008,7(1)：22-25.
[55]陈晓吟等.5一氨基酮戊酸光动力与二氧化碳激光治疗尖锐湿疣的临床疗效观察[J].岭南皮肤性病科杂志,2009,16(4)：262-264.
[56]榻国维.疣毒净治疗尖锐湿疣的多中心临床研究[J].广州中医药大学学报,1998,15(4)：251.
[57]员熙章.员熙章自拟皂甲汤治疗尖锐湿疣200例[J].内蒙古中医药,
[58]冯怡,邓远辉等.鸦胆子抗人乳头瘤病毒的作用研究[J].中成药,2006,28(12)：1819-1820.
[59]李劲等.柴胡对人乳头瘤病毒杀灭作用的实验研究[J].中国中西医结合皮肤性病学杂志,2005,4(3)：171-173.
[60]崔炳南等.复方杠柳液外用治疗尖锐湿疣临床观察及对离体人乳头状瘤病毒DNA的影响[J].中国中西医结合杂志,2005,25(5)：392-396.
[61]Irmler M, Thome M, Hahne M, et al.Inhibition of death receptor signals by cellular FLIP. Nature,1997:388(6638):190-195.
[62]Isacson C, Kessis TD, Hedrick L, et al. Both cell proliferation and apoptosis increases with Lesion grade in cervical neoplasia but not correlate with human papillornavirus type. Cancel Res,1996;56(4):669-674.
[63]李代强,谢季,李美蓉.肺鳞癌及癌前病变PCNA、P16、P21、P53表达及细胞凋亡观察[J].临床试验病理学杂志,2002；18(4)：384-386.
[64]吴明尚.尖锐湿疣抗复发治疗的研究案进展[J].中国医学文摘,2008,17(2)：93-95.
[65]郑小帆.激光治疗79例尖锐湿疣复发的原因探讨[J].中国医学创新,2009,6(17)：80-81.
[66]李宾玲等.中医药治疗尖锐湿疣的研究进展[J].河南中医学院学报,2006,21(124)：86-88.
[67]廖元兴.现代性病诊断与治疗[M].江西科学出版社.2004,2.
[68]刘巧主编.中西医结合治疗性病学[M].北京：人民军医出版社,2001：83-92.
[69]Malerbal, Gribaldo L, Diodovich C, et AI. Induction of apoptosis and inhibition of telomerase activity in human bone marrow and HL-60 p53 null cells treated with anti-cancer drugs. Toxicol In Vitro,2005,19(4):523-532.
[70]Krajewska M, Wang HG, Krajewski S, et al. Immunohistochemical analysis of invivo patterns of expression of CPP32(Caspase-3), a cell death protease. Cancer Res,1997,57 (8):1605-1613.
[71]Ashkenazi A, Dixit VM. Death receptor:signaling and modulation. Science,1998,281(5381):1305-1308.
[72]Ravagnan L,Roumier T,KroemerG. Mitochondria, the killer organelles and their weapons. J Cell Physiol,2002,192(2):131-137.
[73]Boatright KM, Salvesen GS. Mechanism of caspase activation. Curr Opin Cell Biology,2003,15(6):725-731.
[2]周剑波等.人乳头瘤病毒检测及临床应用[J].职业与健康,2008,24(19)：2102-2104.
[3]练霭云.中医药学刊[J].尖锐湿疣发病机理的研究评述,2004,22(5)：895-896.
[4]廖元兴.尖锐湿疣与相似皮肤病的诊断与治疗[M].第一版.江西： 科学技术出版社.2004：159.(著作)
[5]龚向东,叶顺章,张国成等.2000年全国性病流行病学分析[J].中国性病艾滋病防治,2001,7(3)：131—134.
[6]陈志伟.皮肤性病辨治精要[M].北京：人民军医出版社.2007：78-79.(著作)
[7]Matlashewski G, Schneider J, Banks L, et al. Human papillo-mavirus type 16 DNA cooperates with activated ras in transforming primary cells[J]. EMBO J,2005,24(4): 1502-1507.
[8]Marshall K. Cervical dysplasia:early intervention. Alterm Med Rev.2003,8 (2): 156-170.
[9]Munoz N, Bosch FX, de-Sanjose S, et al. Epidemiologie classification of human papillomavirus types associated with cervical cancer. NEngl J Med,2003,348(6): 518-527.
[10]吴志华.现代性病学[M].广州：广东人民出版社.2002：193.
[11]韩国柱.尖锐湿疣研究进展[J].中国麻风皮肤病杂志,2002,18(4)：385-387.
[12]卢勇田.尖锐湿疣国内外诊断治疗的现状和进展[J].中国医学文摘-皮肤科学,2007,24(5)：273-276.
[13]王松挺.中国肛肠病杂志[J].尖锐湿疣的治疗进展,2007,27(9)：45-47
[14]应作霖,吴瑞勤.皮肤病与性病[J].尖锐湿疣患者的免疫功能和免疫治疗研究进展,2006,18(3)：12-15.
[15]Golsteln P.Controling cell death[J]. Science,1997,275(5303):1081-1082.
[16]李晓萍等.鸦胆子治疗尖锐湿疣24例[J].ACPM,2002,12(4)：54-55.
[17]王霄鹏.中国伤残医学[J].贯众散防治尖锐湿疣电灼后复发的临床观察,2008,16(4)：82-83
[18]王凝芳,陈菊梅.传染病学[M].第一版.北京：中国协和医科大学出版社,2000,257-261.(著作)
[19]Morelli AE, Belardi G, Dipaola G, et al. Cellular subsets and epithe - lial ICAM -1 and HLA —DR expression in human papillomavirus infection of the vulva[J]. Acta Derm Venereol.1994,74(1):45-50.
[20]Sheets EE, Yeh J. The role of apoptosis in gynaecological malignancies[J]. Ann Med,1997:29(2):121-126.
[21]Tjalma WA, WeylerJJ, Bogers JJ, et al. The importance of bioligical factors(bcl-2, bax, p53, PCNA, MI HPV and angiogenesis)in invasive crevical cancer[J]. Eur J Obstet Repord Biol,2001;97(2):223-230.
[22]侯孟君,范瑞强等.中药疣毒净对离体人乳头状瘤病毒DNA的影响[J].广州中医药大学学报,1998,15(1)：56-58.
[23]闻玉梅.现代医学微生物学[M].上海：上海医科大学出版社,1999,957-967.
[24]宋丽君等.国外医学妇幼保健杂志[J].尖锐湿疣的免疫学发病机制及免疫治疗进展,2003,14(4)：229-231.
[25]Coleman N, Birley HD, Renton AN, et al. Immunological events in re—gressing genital warts [J]. Am J Clin Pathol.1994,102(6):768-774.
[26]Huang GT, Zhang X, Park NH. Increased ICAM-1 expression in transformed human oral epithelial cells:molecular mechanism and func—tional role in peripheral blood mononuclear cell adhesion and lymphokine— activated—killer cell cytotoxicity[J]. InI J Oncol,2000,17(3):479—486.
[27]刘冬先等.中华皮肤科杂志[J].尖锐湿疣患者外周血CD8+T细胞细胞因子的表达,2007,40(11)：674-675.
[28]刘冬先等.中国皮肤性病学杂志[J].尖锐湿疣患者外周血 CD4+T细胞细胞因子的检测,2007,21(7)：414-415.
[29]马勇刘彤.细胞与分子生物学杂志[J].尖锐湿疣组织中IFN-γ mRNA和IL-4mRNA的表达,2008,24(4)：368-369.
[30]郭庆曾凡钦等.中华皮肤科杂志[J].尖锐湿疣皮损活化抗原CD69、CD38、HLA—DR的表达及其意义,2007,40(9)：543-545.
[31]林友胜,张玉梅.四川医学[J]. PCNA、p53、Ki-67在尖锐湿疣中的表达和意义,2007,28(3)：322-323.
[32]胡野凌志强单小云编著.细胞凋亡的分子医学[M].北京：军事医学科学出版社,2002：335.(著作)
[33]宋今丹等.医学细胞生物学[M].北京：人民卫生出版社,第三版,2004：259.(著作)
[34]劳山 陈罡等.微创医学[J].肿瘤细胞增殖标志物蛋白功能及意义的研究进展,2009,4(3)：273-275.
[35]Szajerka A. Dziegiel P. Szajerka T Immunohistochemical evaluation of metallothionein, Mcm-2 and Ki-67 antigen expression in tumors of the adrenal cortex[J]. Antlcancer Res.2008,28 (5B):2959-2965.
[36]Nishihara K. Shomori K. Fujioka S Minichromosome maintenance protein 7 in colorectalcaneer:impliCafion of prognostic significance[J]. Int J Oncol,2008,33(2): 245—251.
[37]Burger M. Denzinger S. Hartmann A Mcm2 predicts recurrence hazard in stage Ta/T1 bladder cancer more accurately than CK20, Ki67 and histological grade[J]. 2007,96(11):1711-1715.
[38]Ivan T. Tedorov, Brace A. Wemem. dal. HsMCM2/BM28:A novd pmlif erationnlarker for human tumoursand normal tissues.Laboratory Investigation,1998; 78:73—78.
[39]李斌等.中华临床新医学[J].MCM2蛋白表达研究的临床意义,2003,3(10)：907-908.
[40]Williams G H, Romanowski P, Morris L, et al. Improved cervical smear assessment using an tibodies against proteins that regulate DNA replication[J3. Proe Natl Acad Sci USA,1998,95(25):14932—14937.
[41]Freeman A, Morris L S, Mills A D, et al. Minichromosome maintenance proteins as biological markers of dysplasia and malignancy[J]. Clin Cancer Res,1999,5(8):2121—2132.
[42]李艳玲等.中国皮肤性病学杂志[J].尖锐湿疣和鲍温样丘疹病皮损中MCM一2蛋白的检测,2008,22(7)：398-400.
[43]易铁男等.国外医学肿瘤学分册[J]. Caspase家族与细胞凋亡的研究进展,2001,28(1)：39-42.
[44]戴听等.中国现代医药杂志[J].凋亡相关蛋白Caspase研究进展,2010,12(4)：130-132。
[45]祝兴旺,宋彦等.医学临床研究[J].凋亡相关蛋白Livin及Caspase — 3在膀胱移行细胞癌中的表达及临床意义,2008,25(11)：1955-1957.
[46]Takahashi T. Ogo M. Hibino T. Partial purification and characterization of two distinct types of caspases from human epidermis. J Invest Dennatol 1998:111:367—372.
[47]Eckhart L, Ban J, Fischer H, el al. Caspase— 14:analysis of gene structure and mRNA expression during keratinocyte diferentiation. Biochem Biophys Res Commun 2000:277:655—659.
[48]Lippens S, Kockx M, Knaapen M, et al. Epidermal diferentiation does not involve the pmapoptotic executioner caspases, but is associated wi th caspase — 14 induction and processing. Cell Death Diffter 2000; 7:1218 - 1224.
[49]Konstan ti—nidou AE, Givalos N, Gakiopo ulou H, et al. Caspa--3 immunohistochemical expresion is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas. Apoptosis 2006; 5:[Epub ahead of print].
[50]杨戈等.中国麻风皮肤病杂志[J].HPV载量、PCNA和Caspase — 3的表与尖锐湿疣发病相关 性研究进展,2007,23(11)：991-993.
[51]熊芬等.临床及实验研究[J].尖锐湿疣细胞凋亡与caspase - 3、bcl - 2的表达,2006,28(4)：4-6.
[52]尹光文等.中华皮肤科杂志[J].生存素mRNA和Caspase - 3在尖锐湿疣组织中的表达,2006,39(5)：292-293.
[53]魏国等.中国麻风皮肤病杂志[J].消疣煎外洗对CA患者皮损PCNA表达的影响.2006,22(2)：129-130.
[54]李英等.中国中西医结合皮肤性病学杂志[J].祛疣洗剂治疗尖锐湿疣的临床研究及其作用机制,2008,7(1)：22-25.
[55]陈晓吟等.5一氨基酮戊酸光动力与二氧化碳激光治疗尖锐湿疣的临床疗效观察[J].岭南皮肤性病科杂志,2009,16(4)：262-264.
[56]榻国维.疣毒净治疗尖锐湿疣的多中心临床研究[J].广州中医药大学学报,1998,15(4)：251.
[57]员熙章.员熙章自拟皂甲汤治疗尖锐湿疣200例[J].内蒙古中医药,
[58]冯怡,邓远辉等.鸦胆子抗人乳头瘤病毒的作用研究[J].中成药,2006,28(12)：1819-1820.
[59]李劲等.柴胡对人乳头瘤病毒杀灭作用的实验研究[J].中国中西医结合皮肤性病学杂志,2005,4(3)：171-173.
[60]崔炳南等.复方杠柳液外用治疗尖锐湿疣临床观察及对离体人乳头状瘤病毒DNA的影响[J].中国中西医结合杂志,2005,25(5)：392-396.
[61]Irmler M, Thome M, Hahne M, et al.Inhibition of death receptor signals by cellular FLIP. Nature,1997:388(6638):190-195.
[62]Isacson C, Kessis TD, Hedrick L, et al. Both cell proliferation and apoptosis increases with Lesion grade in cervical neoplasia but not correlate with human papillornavirus type. Cancel Res,1996;56(4):669-674.
[63]李代强,谢季,李美蓉.肺鳞癌及癌前病变PCNA、P16、P21、P53表达及细胞凋亡观察[J].临床试验病理学杂志,2002；18(4)：384-386.
[64]吴明尚.尖锐湿疣抗复发治疗的研究案进展[J].中国医学文摘,2008,17(2)：93-95.
[65]郑小帆.激光治疗79例尖锐湿疣复发的原因探讨[J].中国医学创新,2009,6(17)：80-81.
[66]李宾玲等.中医药治疗尖锐湿疣的研究进展[J].河南中医学院学报,2006,21(124)：86-88.
[67]廖元兴.现代性病诊断与治疗[M].江西科学出版社.2004,2.
[68]刘巧主编.中西医结合治疗性病学[M].北京：人民军医出版社,2001：83-92.
[69]Malerbal, Gribaldo L, Diodovich C, et AI. Induction of apoptosis and inhibition of telomerase activity in human bone marrow and HL-60 p53 null cells treated with anti-cancer drugs. Toxicol In Vitro,2005,19(4):523-532.
[70]Krajewska M, Wang HG, Krajewski S, et al. Immunohistochemical analysis of invivo patterns of expression of CPP32(Caspase-3), a cell death protease. Cancer Res,1997,57 (8):1605-1613.
[71]Ashkenazi A, Dixit VM. Death receptor:signaling and modulation. Science,1998,281(5381):1305-1308.
[72]Ravagnan L,Roumier T,KroemerG. Mitochondria, the killer organelles and their weapons. J Cell Physiol,2002,192(2):131-137.
[73]Boatright KM, Salvesen GS. Mechanism of caspase activation. Curr Opin Cell Biology,2003,15(6):725-731.