宫清颗粒对药物流产人早孕绒毛、蜕膜细胞凋亡诱导因素及执行蛋白酶影响的研究
|
摘要
目的:从细胞凋亡角度探讨宫清颗粒防治药流后出血的机理。
方法:将180例药物流产患者随机分为宫清颗粒组60例(药流第一天即加服宫清颗粒)、茜芷胶囊组60例(药流第一天即加服茜芷胶囊)及药流对照组60例(单纯口服米非司酮与米索前列醇),观察用药后的临床疗效。同时设人工流产组60例。在观察疗效的同时,获取各组早孕绒毛、蜕膜组织,运用电镜技术及免疫组化、原位杂交、琼脂糖凝胶电泳法等先进方法,从形态学、分子及基因水平观察取材组织的电镜形态学改变、PR(孕激素受体)、EGF(表皮生长因子)、EGFR(表皮生长因子受体)、凋亡执行蛋白酶casepase-3、caspase-8及其mRNA的表达情况及其各指标间相互关系。
结果:宫清颗粒组孕囊排出时间优于茜芷胶囊组和药流对照组,差异均有非常显著性(P<0.01);宫清颗粒组药流后阴道出血量、少于茜芷胶囊组,差异均具有显著性(P<0.05);宫清颗粒组药流后阴道出血量、出血时间少于药流对照组,差异均具有显著性(P<0.01或P<0.05)。绒毛、蜕膜电镜形态学观察表明,宫清颗粒组呈现明显凋亡表现;宫清颗粒组琼脂糖凝胶电泳出现明显DNA梯形条带;宫清颗粒组药流后绒毛PR、EGF、EGFR表达较其他三组明显降低,差异均具有显著性(P<0.05);宫清颗粒组药流后蜕膜PR、EGF、EGFR表达较其他三组明显降低,差异均具有非常显著性(P<0.01);宫清颗粒组药流后绒毛、蜕膜组织caspase-3、caspase-8及其mRNA表达较其他三组明显增加,差异均具有显著性(P<0.05)。
结论:宫清颗粒能下调PR在绒毛和蜕膜组织的表达,促进绒毛滋养细胞和蜕膜组织变性、坏死及凋亡,使残留绒毛、蜕膜组织尽快排出体外而防治药物流产后出血;宫清颗粒能下调EGF、EGFR在绒毛和蜕膜组织的表达,抑制其促增生、分化的作用,诱导发生受体介质功能紊乱和抑制,促进绒毛滋养细胞和蜕膜组织变性、坏死及凋亡而防治药物流产后出血;宫清颗粒能上调casepase-3、caspase-8在绒毛和蜕膜组织的表达,通过细胞膜途径,促进滋养层细胞和蜕膜组织凋亡增加而防治药物流产后出血。且宫清颗粒的临床疗效和对药物流产后人早孕绒毛、蜕膜细胞凋亡相关指标的改善明显优于茜芷胶囊。
Objective: To investigate the effects of Gongqing grain on the expressions of induced factor and regulating protein of the apoptosis in villi and decidua in hemorrhage after human early medical abortion .
Method: 180 patients were divided into three groups randomly on their owns accord:the GongQing grain group (n=60,taking GongQing grain at the first day of the medical abortion),QianZhi capsule group(n=60,taking QianZhi capsule at the first day of the medical abortion), the medical abortion group(n=60,only taking mifepristone and misoprostol) ,and artificial abortion group(n=60)was set.Symptoms and signs of each group were observed before and after treatment.Meanwhile villi and deciduas of each group were collected. The experiment utilized electronic microscopic technique,and applied advanced methods of im-munohistochemica、insituhybridization and DNA agarose gel electrophoresis to observe the expressions of epidermal growth factor(EGF)、epedermal growth factor receptor(EGFR)、progesterone receptor(PR)、regulating protein (caspase-3、8)and the change of their mRNA in the villi and deciduas in early medical abortion.
Results: There was significant difference between GongQing grain group with the QianZhi capsule group and the medical abortion group in the blastocyst discharged time, the period and the amount of lochia ( P<0.05/P<0.01). The electronic microscopic observed indicated distinct change of apoptosis in the GongQing grain group. The obvious DNA ladder was observed in the decidual tissue and chorionic villi in Gong Qing grain group.The level of PR、EGF and EGFR in the villi and deciduas decreased more significantly in the GongQing grain group than the other three groups(P<0.05/P<0.01). The level of caspase-3、8 and the changes of their mRNA increased more significantly in the GongQing grain group than the other three groups(P<0.05).
Conclusion: It was speculated that GongQing grain resisted early pregnancy because it suppressed the expression of PR、EGF、EGFR,it improved the expression of caspase-3、8and their mRNA in chorionic villi and deciduas. These was its possible scheme that it could shorten the duration of vaginal bleeding after medical abortion.
方法:将180例药物流产患者随机分为宫清颗粒组60例(药流第一天即加服宫清颗粒)、茜芷胶囊组60例(药流第一天即加服茜芷胶囊)及药流对照组60例(单纯口服米非司酮与米索前列醇),观察用药后的临床疗效。同时设人工流产组60例。在观察疗效的同时,获取各组早孕绒毛、蜕膜组织,运用电镜技术及免疫组化、原位杂交、琼脂糖凝胶电泳法等先进方法,从形态学、分子及基因水平观察取材组织的电镜形态学改变、PR(孕激素受体)、EGF(表皮生长因子)、EGFR(表皮生长因子受体)、凋亡执行蛋白酶casepase-3、caspase-8及其mRNA的表达情况及其各指标间相互关系。
结果:宫清颗粒组孕囊排出时间优于茜芷胶囊组和药流对照组,差异均有非常显著性(P<0.01);宫清颗粒组药流后阴道出血量、少于茜芷胶囊组,差异均具有显著性(P<0.05);宫清颗粒组药流后阴道出血量、出血时间少于药流对照组,差异均具有显著性(P<0.01或P<0.05)。绒毛、蜕膜电镜形态学观察表明,宫清颗粒组呈现明显凋亡表现;宫清颗粒组琼脂糖凝胶电泳出现明显DNA梯形条带;宫清颗粒组药流后绒毛PR、EGF、EGFR表达较其他三组明显降低,差异均具有显著性(P<0.05);宫清颗粒组药流后蜕膜PR、EGF、EGFR表达较其他三组明显降低,差异均具有非常显著性(P<0.01);宫清颗粒组药流后绒毛、蜕膜组织caspase-3、caspase-8及其mRNA表达较其他三组明显增加,差异均具有显著性(P<0.05)。
结论:宫清颗粒能下调PR在绒毛和蜕膜组织的表达,促进绒毛滋养细胞和蜕膜组织变性、坏死及凋亡,使残留绒毛、蜕膜组织尽快排出体外而防治药物流产后出血;宫清颗粒能下调EGF、EGFR在绒毛和蜕膜组织的表达,抑制其促增生、分化的作用,诱导发生受体介质功能紊乱和抑制,促进绒毛滋养细胞和蜕膜组织变性、坏死及凋亡而防治药物流产后出血;宫清颗粒能上调casepase-3、caspase-8在绒毛和蜕膜组织的表达,通过细胞膜途径,促进滋养层细胞和蜕膜组织凋亡增加而防治药物流产后出血。且宫清颗粒的临床疗效和对药物流产后人早孕绒毛、蜕膜细胞凋亡相关指标的改善明显优于茜芷胶囊。
Objective: To investigate the effects of Gongqing grain on the expressions of induced factor and regulating protein of the apoptosis in villi and decidua in hemorrhage after human early medical abortion .
Method: 180 patients were divided into three groups randomly on their owns accord:the GongQing grain group (n=60,taking GongQing grain at the first day of the medical abortion),QianZhi capsule group(n=60,taking QianZhi capsule at the first day of the medical abortion), the medical abortion group(n=60,only taking mifepristone and misoprostol) ,and artificial abortion group(n=60)was set.Symptoms and signs of each group were observed before and after treatment.Meanwhile villi and deciduas of each group were collected. The experiment utilized electronic microscopic technique,and applied advanced methods of im-munohistochemica、insituhybridization and DNA agarose gel electrophoresis to observe the expressions of epidermal growth factor(EGF)、epedermal growth factor receptor(EGFR)、progesterone receptor(PR)、regulating protein (caspase-3、8)and the change of their mRNA in the villi and deciduas in early medical abortion.
Results: There was significant difference between GongQing grain group with the QianZhi capsule group and the medical abortion group in the blastocyst discharged time, the period and the amount of lochia ( P<0.05/P<0.01). The electronic microscopic observed indicated distinct change of apoptosis in the GongQing grain group. The obvious DNA ladder was observed in the decidual tissue and chorionic villi in Gong Qing grain group.The level of PR、EGF and EGFR in the villi and deciduas decreased more significantly in the GongQing grain group than the other three groups(P<0.05/P<0.01). The level of caspase-3、8 and the changes of their mRNA increased more significantly in the GongQing grain group than the other three groups(P<0.05).
Conclusion: It was speculated that GongQing grain resisted early pregnancy because it suppressed the expression of PR、EGF、EGFR,it improved the expression of caspase-3、8and their mRNA in chorionic villi and deciduas. These was its possible scheme that it could shorten the duration of vaginal bleeding after medical abortion.
引文
[1]经小平,翁梨驹,董白桦,等.诚年月泰用于药物流产的临床观察[J].中国计划生育学杂志,2001;66(2)∶104-106.
[2] Morrison DK, Kaplan DR, Rapp U,eral. Signal transduction from membrane to cytoplasm growth and membrane bound oncogene products increase Raf-1phosphorylation and associated protein kinase activity. Proc Natl Acad Sci,1998;85:8855.
[3] Akcali KC,Khan SA,Moulton BC.Effect of decidualization on the expression of bax and bcl-2 in the rat uterine endometrium.Endocrinology,1998;137:3123-3131.
[4] Wang Z. Prevent from bleeding after medical abortion through prolonged application of mifepristone with misoprostol for terminating early pregnancy. Chin J Obstet Gynecol,2000;35(9):554-557.
[5]刘瑞芬,刘文琼,王玉玲.宫清方防治药物流产后阴道出血及对绒毛超微结构变化的影响[J].福建中医药,2003;34(1):12-14.
[6]栾继红.药物流产后出血副反应的防治与研究进展.湖南中医药导报,2003;9(9):43～44
[7]许梅芬,金毓翠,岑幻仙,等.药物流产后子宫刮出物的组织学观察.中华妇产科杂志,1994;29(12)739～741.
[8]房敬燕,路欣,诸定寿.药物流产后子宫刮出物的组织病理学和免疫细胞化学研究.首都医科大学学报,1999;20(2):89～91.
[9]陈兴林,陈常佩,芦劲,等.经阴道彩色多普勒对药物终止早孕子宫出血时间延长的临床观察与分析.中国超声医学杂志,1998;14(9):38～40
[10]莫凌昭.药流后阴道出血原因分析[J].华夏医学,1999;12( 2):98
[11] Spitz IM, Bardin CW. Clinical phamacology of RU486 an docrRev 1993,14:133
[12]黄丽丽,石一复,陈小端,等.米非司酮抗早孕蜕膜雌孕激素受体的免疫组织化学研究[Jl.中华妇产科杂志,1999;34(5):18-20
[13]夏革清,熊雅丽,孙永玉.米非司酮对早孕绒毛和蜕膜组织中端粒酶的影响[J]生殖医学杂志,2004;13(3):150-152
[14] Schwartzman RA,CidioWski JA Apoptosis the biochemistry and molecular biology of programmed cell death[J].En docrRev,1993;14:133
[15]何丽霞,曲陆荣,陈桂兰,等.米非司酮对人早孕蜕膜组织细胞凋亡的影响[J].生殖与避孕,1999;19(4): 216-219
[16] Welsh AO , Endoer AC.Trophoblast cell interaction and establishment blood circulation in the parictal yolk ration of the rats [J]. Anat Res,1987; 217:203
[17] Parr EL.Apoptosis as the mode of uterine epithelial celldeath during embryo implantation in mice and rats[J].Bio1 Reprod,1987; 36:211
[18]杨业洲,曹泽毅,韩宇研,等.米非司酮对人早孕绒毛细胞增殖和凋亡的影响[J].中华妇产科杂志,1998;33(5): 268-270
[19]张月莲,陈贵安,刘以训,等.正常与药物流产绒毛蜕膜组织细胞凋亡及相关基因的表达[J].中华妇产科杂志,2002;37(4): 220-222
[20]宋淑芳,宋静慧,等.米非司酮药物流产阴道出血原因探讨.内蒙古医学院学报,2006;28(3):181～184
[21]曹泽毅.中华妇产科学,北京:人民卫生出版社,2005;第2版:2852.
[22] Mirakian R,Nye K,Palazzo FF,et al. Methods for detecting apoptosis in medical abortion. J Immunol Methods,2002;265:161-175.
[23]杨雪峰,任芬若,白桦,等.米非司酮对早孕蜕膜及绒毛中雌孕激素受体的影响[J].中国实用妇科与产科杂志中,2000;16(10):605-606.
[24] Ruzycky F,Csagranda F,Audero E,et al. Differential expression of protein kinase cisoforms in the human placenta,1998;17(7):461.
[25]孙晓燕,郑岗.米非司酮对早孕绒毛组织EGFR、C-myc蛋白表达的影响[J].西安医科大学学报(医学版),2002;23(6):569-572.
[26]张玉珍.中医妇科学.北京:中国中医药出版社,2002,第一版:350-351.
[27]刘瑞芬,王丽娟.从虚热瘀论治药流后恶露不绝.山东中医杂志,2004;23(1):9～10
[28]刘文琼.中医防治药物流产后阴道出血概况.山东中医药大学学报,2001;25(1):74-76
[29]于燕,王秀霞,刘红梅,等.生化止血饮对药物流产后大鼠子宫蜕膜中FN与LM的影响[J].中国中医药科技,2004;11(4):216-7.
[30]赵瑞华.复元冲剂防治药物流产后出血的临床和实验研究[J].中国中医药科技,2004;11(4): 200- 2
[31]周幸,白世泽,李新生,等.血停灵冲剂的药效学研究[J].中国中医药科技,1997;4(5):271-272
[32]王洪萍,刘瑞芬,等.宫清颗粒治疗药物流产后阴道出血150例临床观察.中国计划生育学杂志,2005;116(6):365-367
[33]刘文琼,刘瑞芬,赵洁.宫清方防治药物流产后阴道出血临床观察.山东中医药大学学报,2003;27(1):32-36
[34]王洪萍.宫清颗粒在药物流产中作用机制探讨.中国新药与临床杂志,2007;26(1):52-55
[35]刘瑞芬,刘文琼.宫清方防治药物流产后阴道出血及对绒毛超微结构变化的影响.福建中医药,2003;34(1):12～13
[36]曹泽毅.中华妇产科学,北京:人民卫生出版社,1999;第1版:2588.
[37]上海市卫生局.妇产科诊疗常规,上海:上海科学技术出版社,1999,第1版:300.
[38]中华人民共和国卫生部.中药新药临床研究指导原则.第一辑,1993,231.
[39]沈稚琴,黄稚萍.月经血量测定的方法学和临床应用[J].陕西医学检验,1995;10(2):5-7
[40]张玉珍.中医妇科学,北京:中国中医药出版社,2002,第1版:352.
[41]张翠萍.固冲清宫汤治疗药物流产后出血过多48例.安徽中医学院学报,1994;13(1):23.
[42]卓毅.清宫逐瘀汤治疗108例米非司酮流产后阴道出血的临床观察.四川中医,1995;(1):36.
[43]吕大鸣,刘秀云.益气冲化汤治疗药流后阴道出血60例[J].中医药信息,2004;21(3): 3
[44]吴昌生.辨证治疗流产后恶露不绝113例小结.安徽中医学院学报,1991;10(2):35
[45]刘青云.中药药理学[M]北京:人民卫生出版社,1997:146-149.
[46]曲淑岩.马齿苋的药理及临床应用.吉林中医药.1985;(3):28.
[47]郑俊华.生药学[M].北京:人民卫生出版社,2002:235-240.
[48]王裕生.中药药理与应用.北京:人民卫生出版社,1983;第1版:1169.
[49]郭月芳,金祖汉,杨明华,等.宫清颗粒调经及抑菌作用研究.基层中药杂志,2001;(15)6:7-8
[50]李培植.中药益母草对小白鼠抗着床和抗早孕作用的初步研究.西安医科大学学报,1988;9(4):317.
[51]张秀成.抗生育中草药[M].北京:北京科学技术出版社,1994:72, 66, 80.
[52]宋树立.川牛膝水煎液影响小鼠妊娠的实验研究.中国医药学报,1994;9(4):40.
[53]南京药学院编.中草药学.南京:江苏科学技术出版社,1980,第1版:296.
[54]刘寿山主编.中药研究文献摘要(1962-1974).北京:科学出版社,1979:581
[55]陈振中,刘莉,李群爱,等.蒲黄的实验研究.湖南区药杂志,1984;11(2):29
[56]梁从云,王世忠,张磊,等.中药党参对异质性荧光染色的巨噬细胞功能的影响.中医药学报,1995;10(6):45
[57]王裕生主编.中药药理与应用.北京:人民卫生出版社,1983:898.
[58]李广勋.中药药理毒理与临床.天津:天津科技翻译出版公司,1992:365.
[59]郭月芳,金祖汉,杨明华,等.宫清颗粒活血祛瘀药效学研究.中成药,2002;24(8):607-609
[60] Spitz IM, Bardin CW. Clinical pharmacology of RU 486-An antiprogestin and antiglucocorticoid [J].Contraception, 1993;48: 403
[61] Vaishnaw AK,McNally JD,Elkon KB.Apoptosis in the rheumatic diseases[J]. Arthritis Rheum,1997;40;1917-1927
[62]龚非力,沈关心,李卓娅,等.医学免疫学[M] .上海科学技术出版社,2000:6.
[63]席娜.细胞凋亡与流产.四川医学,2005;26(7):803-805.
[64] Halperin R,Peller S,Rotschild M, et al. Placental apoptosis in normal and abnormal pregnancies. Gynecol Obstet Investiga,2000;50:84-87.
[65] Thiet MP, Suwanvanichkij V, Hasselblatt K, et al. Apoptosis in human term placenta. A morphological and expression study. Gynecol Obstet Investiga,2000;50:88-91.
[66] Kokawa K, Shikone T, Nakano R, et al. Apoptosis in human chorionic villi and deciduas during normal embryonic development and spontaneous abortyion in the first trimester [J].Placenta ,1998;19(1):21～26
[67] Moulton BC. Transforming growth factor stimulates endometial stromal apoptosis in witor. Endorcinology,2002;14:133-151.
[68]杨业洲,曹泽毅,韩字研等.米非司酮对人早期妊娠绒毛细胞增殖和凋亡的影响[J].医学科技,1997;1(1): 3-6
[69]刘颖,冯霞.米非司酮促进早孕绒毛及蜕膜细胞凋亡的研究[J].徐州医学院学报,2001;21(3):218～220.
[70] Anjum R,Khar A. Differential regulation of apoptosis in AK-5 tumor cells by the proto- oncogene Bcl-2: presence of Bcl-2 dependent and independent pathways. FEBS Lett, 2001;499(1-2):166-170.
[71] Shi WL,Wang JD, Fu Y, etal. The effect of RU486 on progesterone eceptor in villous and extravillous trophoblast. Hum Reprod,2001;10:953-958.
[72]席娜,刘宏伟,许良智,等.三苯氧胺联合米非司酮药物流产对早孕绒毛细胞凋亡及调控基因的影响.生殖与避孕,2005;25(11):696～699
[73]杜群,王汝俊,徐勤.活血化瘀中药对慢性萎缩性胃炎大鼠细胞增殖及凋亡的研究[J] . 2003;20(2):136-139.
[74]陈培丰.清热解毒法诱导肿瘤细胞凋亡的研究[J].浙江中医学院学报,2003;27(1):12～15.
[75]曹立幸,李泽民,李同玺.益气养血、固肾安胎法治疗肾虚流产保胎作用机理研究,2004;19(2):53～54.
[76]陈惠新,许岸高,刘集鸿.黄参方剂诱导胃癌癌前病变细胞凋亡和影响BCL-2蛋白表达的研究[J].陕西中医,2001;22(7):438-440.
[77]彭黎明,王曾礼.细胞凋亡的基础与临床[M].北京:人民卫生出版社,2000:153.
[78] Spitz IM,Bardin CW.Clinical pharmacology of RU486-An antiprogestin and antiglucocortucoid[J].Contraception,1993;48:403
[79]刘德培,查锡良,药立波,等.医学分子生物学[M].2003:528
[80]金力,沈维雄,孙志达,等.复方米非司酮对人早孕蜕膜组织雌孕激素受体的影响.生殖与避孕,2000;20:202-207.
[81]杨雪峰,任芬若,白桦,等.米非司酮对早孕蜕膜及绒毛中雌孕激素受体的影响.中国实用妇科与产科杂志,2000;16: 605-606.
[82]张立会,胡秀英,李荷莲,等.米非司酮对人蜕膜及绒毛膜雌、孕激素受体的影响.白求恩医科大学学报,1999;25: 731-732.
[83]黄丽丽,石一复,陈小瑞,等.米非司酮抗早孕蜕膜雌、孕激素受体的免疫组织化学研究.中华妇产科杂志,1999;34: 275-277.
[84]宋淑芳,宋静慧,等.米非司酮药物流产阴道出血原因探讨.内蒙古医学院学报2006;28(3):181～184
[85] Mirakian R,Nye K,Palazzo FF,et al. Methods for detecting apoptosis in medical abortion.J Immunol Methods,2002;265:161-175.
[86] zaytseva ts, goncharova vn, morozova ms, et al. the effect of ru486 on progesterone and oestrogen receptor concentrations in human decidua on early pregnancy. hum reprod, 1993;8:1288-1292.
[87] hill ncw, rivera j, bernal al, et al. the effect of ru486 on progesterone and oestrogen receptor concentrations in the decidua and placenta in early pregnancy. hum reprod, 1990;5:464-467.
[88]曹泽毅.中华妇产科学,北京:人民卫生出版社,2005,第2版:2852.
[89]王宏.国外医学免疫学分册,1995,3:146-148.
[90] Murray JF,Dowing JA,Evans c et al.J Endocrinol,1993;137(2):253-264
[91] Orwitz ER, Robinson JN,Repke JT.Ihe initiation of parturition: A comparative analysis Across the species. Curr Probl Obstet Gynecol Fertil, 1999;22: 46-71.
[92]张丽凤,苏应宽,盖凌,等.表皮生长因子受体在子宫内膜、早孕蜕膜及滋养细胞中的表达[J].中华妇产科杂志,1999;34(6):357-359.
[93] Piva M, Flieger,O Rider V. Growth factor control of cultured rat uterine stromal cell proliferation is progesterone dependent[J].Bio Reprod, 1996;55(6):1333-1342.
[94] Eldadah BA, Faden AI. Caspase pathways, neuronal apoptosis, and CNS injury. J Neurotrauma,2000;17(10):811-829.
[95] Zhang X M .The focuses in the researches of apoptosis[J].Chin J Pharmacol Toxicol(中国药理学与毒理学杂志),2000;14(2):81-85.
[96] Raff M.Cell suicide for beginners[J].Nature,1998;396(6707):119-122
[97] Kumar S. The apoptotic cysteine protease CPP32.Int J Biochem Cell, 1997;29 (3):393-396.
[98] Enari M,Sakahira H,Yokoyama H,et al.A caspase activated DNase that degrades DNA during apoptosis,and its inhibiter ICAD[J].Nature,1998;391(6662):43-50.
[99] Slee EA, Keogh SA, Martin SJ.Cleavage of BID during cytotoxic drug and UV radiation-induced apoptosis occurs downstream of the point of Bcl-2 action and iscatalysed by caspase-3:a potential feed-back loop for amplification of apoptosis-assciated[J].Cell Death Differ,2000;7(6): 556-565.
[100] Huppertz B, Frank HG, Reister F, et al.Apoptosis cascade progr- esses during turnover of human trophoblast:analysis of villous cytotropho- blast and syncytial fragments in vitro.Lab Invest,1999;79(12):1687-1702.
[101] ThornberryNA, LazebnikY.Caspases: Enemieswithin[J].Science,1998; 281 (8): 1312-1316.
[102] Wallach D. Suicide by order:some open questions about the cell killing activities of the TNF ligand and receptor family.Cytokine Growth Factor Reviews ,1996; 7(3):211～221.
[103] Luo X, Budihardjo I, Zou H, et al. Bid, a Bcl-2 interacting protein, mediates cytochrome release in response to activation of cell surface death receptors . Cell,1998;94(4):481-490.
[104] Li H, Zhu H, Xu CJ,et al.Cleavage of BID by Caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell, 1998; 94:491-501.
[105] Li H,Yan J.Deciphering the pathways of life and death.Curr Opin Cell Biol, 1999;11:261-266.
[106] Schulze Osthoff K, Ferrari D, Los M, et al.Apoptpsis signaling by death eceptors.Eur J Biochem, 1998;254:439-459.
[107] Heiskanen KM, Bhat MB HW, et a1.Mitochondrial depolarization accompanies cytochrome c release during apoptosis in PC6 cells. JBiol Chem, 1999;274: 5654-5658.
[1]蒋惠贞.活血化瘀法对药物流产后HCG水平下降伴出血不止的疗效观察[J] .新中医,1995;27(9):24.
[2]胡洪瑞.固经灵治疗药物流产后出血30例[J] .新中医,1996; 23 (2):20.
[3]卞宜心.宫清方治疗药物流产后出血过多127例[J].浙江中医杂, 1996; 31(7): 299.
[4]王学瑞.中药治疗药物流产出血的疗效观察[J].中医杂志,1993;34(8):491.
[5]吕大鸣,刘秀云.益气冲化汤治疗药流后阴道出血60例.中医药信息,2004; 21(3): 3.
[6]王淑善、王少华.用消补兼施法治药流后恶露不止的经验.辽宁中医杂志, 1999; (10)436-8.
[7]张婷婷.中药祛膜肠治疗药物流产后出血214例临床与实研究.中国中西医结合杂志,1997;(9)534-6.
[8]何晓虹.生化汤治疗药物流产后恶露不绝197例观察.时珍国医国药,2001;(9): 828.
[9]孙建新,王玲.辨证论治药流后出血.甘肃中医,2002;15(6):63-4.
[10]王佩.药物流产后阴道出血的中医辨证治疗.甘肃中医学院学报,2003;20(2): 24-5.
[11]王桐生,彭珊英,龙子江.药物流产后出血的中药治疗研究近况.承德医学院学报, 2001;18(2):160-3.
[12]梁晶.药物流产后诸证的中医辨证.四川中医药学报,1997;15(2):29.
[13]王桂芳.化瘀清宫汤治疗药物流产后出血180例[J].实用中医药杂志,2001;17(4):12.
[14]叶铤.生化逐瘀汤防治药物流产后出血的临床观察[J].现代中西医结合杂志,2004;13(8) : 16.
[15]马淑秀.参芪生化汤加味药流后阴道流血Go[J].辽宁中医杂志.1998;25(2): 73.
[16]刘志芬.益气清宫汤治疗药流后出血不止[J].四川中医,1998;16(2):42.
[17]刘凤英.芪蒲坤舌汤治疗药物流产后恶露不绝31例[J].广西中医药,1994;17(4):I 5.
[18]杨景海.参芪当坤汤治疗药物流产后阴道出血29例[J].光明中医杂志,1997;(3):29.
[19]应苹.芩酱缩宫汤缩短药物流产后阴道出血时间160例临床观察[J].中医杂志,1999;40(2):22.
[20]谢鸣.中药辅助米非司酮终止早孕的疗效观察[J].中华妇产科杂志,1996;31(6):373.
[21]张琼芳.清宫止血饮治疗药物及入工流产后出血[J].中国医药学报,1995;10(6):29.
[22]王佩期.固阴煎治疗药物流产后顽固性子宫出血34例[J].实用中医药杂志, 1998;5(14):5.
[23]戴雨红.固冲汤治疗药物流产后持续出血89例.实用中药杂志[J],1999;15(8):34.
[24]张琼,薛赛琴,姜坤.宫腹康胶囊治疗药物流产术后子宫出血的临床研究[J].中药新药与临床药,2001;12(5):318-320
[25]石礼红,张宏丽,李静芳.四物合剂治疗药流后出血[J].江西医学院学报,2002; 42(1):116.
[26]郭小莺.妇血康治疗药物流产后出血100例[J].福建中医药,2001;32(2): 48-9.
[27]冷观群.益母片治疗药物流产后阴道出血98例疗效分析[J].中国中医急症,2001;10(2):28.
[28]孙磊.云南白药减少药物流产后出血80例分析[J].中国计划生育学杂志,1999;7(4):173.
[29]李国辉.自拟妇乐散外敷治疗药物流产后持续出血25例临床观察[J].中医外治杂志,1999;6(3):17.
[30]潘秀群,陈济民.中药内服加外用治疗药物流产后出血不止124例[J].吉林中医药,1999;19(3) : 33- 34.
[31]赵荣胜,等.产乐冲剂减轻药物流产后出血的临床与实验研究[J].中国计划生育学杂志,1998; (3):108-111.
[32]严福生,谢小云,黄晓翘,等.清宫汤协助药物流产的临床与实验研究[J].安徽中医学院学报,2003;22(5)23-26.
[33]王晓东,赵军宁,张自嘉,等.宫复安对子宫的药理作用研究[J].中药药理与临床,1999;15(1):33.
[34]于燕,王秀霞,刘红梅,等.生化止血饮对药物流产后人鼠子宫蜕膜中FN与LM的影响[J].中国中医药科技,2004;11(4): 216-7.
[1] Vaishnaw AK, McNally JD, Elkon KB .Apoptosis in the rheumatic diseases [J].Arthritis Rheum,1997;40:1917-1927.
[2]李翠兰,胡章和,曹来英,等.正常妊娠中细胞增殖细凋亡情况的研究[J].中国实用妇科和产科杂志,2001;6(4):223～224.
[3] Smith SC, Bakcr PN, Symonds EM .Plaental apoptosis in normal human pregnancy[J].AmJ Obstet Gynaecol,1997;177(1):57- 65.
[4] Kokawa K, Shikone T, Nakano R, et al.Apoptosis in human chorionic villi and deciduas during normal embryonic development and spontaneous abortyion in the first trimester[J].Placenta ,1998;19(1):21～26.
[5]杨业洲,曹泽毅,韩字研,等.米非司酮对人早期妊娠绒毛细胞增殖和凋亡的影响[J].医学科技,1997;1(1): 3-6.
[6]刘颖,冯霞.米非司酮促进早孕绒毛及蜕膜细胞凋亡的研究[J].徐州医学院学报,2001;21(3):218～220.
[7] SMITH S C,BAKER P N,SYMONDS E M.Placental apoptosis in normal human pregnancy[J].Am J ObsterGynecol,1997;177:57.
[8]刘德培,查锡良,药立波,等.医学分子生物学[M].2003:528.
[9]丁峰,傅国强,邢福棋,等.米非司酮对人早孕期蜕膜细胞凋亡及其调控基因bcl- 2/bax的影响[J].现代妇产科进展,2002;11(1): 36- 38.
[10]高红军,代解杰等,Bax/Bcl-2mRNA在恒河猴药物流产胎盘中的表达.生物技术,2005;15(2):21-24.
[11] Cheng EHY,David G,Kirsch,et al.Conversion of Bcl-2 to a bax-like death dffector by caspases[J].Science,1997;278(5354):1966-1968.
[12] Raff M.Cell suicide for beginners[J].Nature,1998;396(6707):119-122.
[13] Enari M,Sakahira H,Yokoyama H,et al.A caspase activated Dnase that degrades DNA during apoptosis ,and its inhibiter ICAD[J]. Nature, 1998;391(6662):43-50.
[14] Slee EA, Keogh SA, Martin SJ.Cleavage of BID during cytotoxic drug and UV radiation-induced apoptosis occurs downstream of the point of Bcl-2 action and is catalysed by caspase-3:a potential feed-back loop for amplification of apoptosis-assciated[J].Cell Death Differ, 2000; 7(6): 556-565.
[15]唐旭东,周客元,蔡康荣.高三尖杉脂碱通过激活caspase-3诱导鼻咽癌细胞凋亡[J].细胞与分子免疫学杂志,2002;18(4):366-368.
[16]杜红俊,惠延年,王雨生,等.caspase-3在柔红霉素诱导的人视网膜色素上皮凋亡中的作用[J].第四军医人学学报,2001;22(7):609-611.
[17]李刚,陈必良,米非司酮对早孕绒毛滋养层细胞Bcl-2和caspase-3表达的影响.ISSN 1007-8738细胞与分子兔疫学杂志(Chin.J Cell Mol Immunol) 2003;19(2):136-137.
[18] Wallach D. Suicide by order:some open questions about the cell killing activities of the TNF ligand and receptor family.Cytokine Growth Factor Reviews, 1996;7(3):211～221.
[19] Luo X, Budihardjo I, Zou H, et al. Bid, a Bcl-2 interacting protein, mediates cytochrome release in response toactivation of cell surface death receptors .Cell,1998;94(4):481-490.
[20] Li H, Zhu H, Xu CJ,et al.Cleavage of BID by Caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis.Cell,1998,94: 491-501.
[21] Schulze Osthoff K,Ferrari D,Los M,et al. Apoptosis signaling by death receptors.Eur J Biochem, 1998;254: 439-459i.
[22]周春,董迪荣等.诊断超声照射对人早孕绒毛细胞Caspase 3,8蛋白表达的影响.中国超声医学杂志,2005;21(4):256-258.
[23] Medena JP,Scaffidi C,Kischkel ME,et al.FLICE is activated by association with the CD95 death-inducing signaling complex [J].EMBO J,1997;16:2794.
[24] Hammer A, Blaschitz A,Daxbock C,et al .Fas and Fas-ligand are expressed in the utero placental unit of first-trimester pregnancy[J].AmJReprod Immunol,1999; 41(1):41～45.
[25]杨业洲,韩字研,曹泽毅,等.米非司酮对人早期妊娠绒毛ICE、Fas表达的影响[J].华西医大学报,1998;29(2):216- 219.
[26] Ejima K, Koji, Tsuruta D,et al.Induction of apoptosis inplacentas of pregnant mice exposed to lipopolysacharides: possible invovement of Fas/Fas ligand system[J].Biol reprod, 2000;62(1):178-185.
[27]张月莲,陈贵安等.正常与药物流产绒毛蜕膜组织细胞调亡及相关基因的表达[J].中华妇产科杂志,2002;37(4):220-223.
[28] Moore ED,Ring M,Scriven DR, et al. The role of protein kinase Cisozymes in bombesin-stimulated gastrin rlease from human antral gastrin cells J Biol Chem,1999;274:22493.
[29] Heagerty .AM,Ollerenshaw JD. The phosphoinositide signaling system and hypertension.J Hypertens,1987;5:51.
[30] Stariha RL,Kim SU.Protein kianse C and mitngenantivated protein kinase signaling in oligodendrocytes. Microse Res Tech,2001;52:680.
[31]赖仁胜,周溶等.米非司酮影响早孕滋养细胞的信号传导和凋亡的机制研究.中国实用妇科与产科杂志,2000;16(10)599-601.
[32]朱瑾,周剑萍.c-myc基因mRNA在小鼠胚胎着床期间的表达.生殖与避孕,2001;21(2):77-81.
[33] Pfeifer-Ohlsson S, Goustin AS, Rydnert J, et al. Spatial and temporal pattern of cellular myc onconene expression in developing human placenta: implications for embryonic cell proliferation. Cell, 1984;38: 585-596.
[34] Orwitz ER, Robinson JN, Repke JT.Ihe initiation of parturition: A comparative analysis Across the species. Curr Probl Obstet Gynecol Fertil, 1999,;22: 46-71.
[35] MaruoT,MatsuoH,OtaniT,etal:Role of epidermal growth factor and its receptor in the development of human placenta. Reprod Fertil Dev, 1995; 7(6):1465-1470.
[36]张丽凤,苏应宽,盖凌,等.表皮生长因子受体在子宫内膜、早孕蜕膜及滋养细胞中的表达[J].中华妇产科杂志,1999;34(6):357-359.
[37]付小锁,张景艳.表皮生长因子对人早孕滋养层细胞孕酮分泌的影响.锦州医学院学报,2002;23(2)13～15.
[38]张晶,夏思菊,张建国.米非司酮对早孕蜕膜肿瘤坏死因子-α及转化生长因子-β表达的影响[J].中华妇产科杂志,2001;36 (1): 27-29.
[39] Feinberg RF, Kliman H.I Wang CL Transfoming growth factorbeta stimulates trophoblast oncofetal fibronectin synthesis in vitra implicalions for trophoblast implantation in viVo[J].J Clin Endocrinol Metab, 1994;78( 5): 1241-1248.
[40]金莉萍,邵敬於,李大金,等.米非司酮对早孕蜕膜与绒毛转化生长因子-β基因表达及血清肿瘤坏死因子-α的影响[J].生殖与避孕,2003;23(1):26- 30.
[41]刘纹琰,刘延,刘晓瑗.上海交通大学学报(医学版).早孕药物流产绒毛和蜕膜组织TGF-β1的表达,2006;26(12):1365-1368.
[42] Okuda K,Sakumoto R. Multiple roles of TNF super family members in corpus luteum function .Reprod Biol Endoc, 2003; 10(1):95.
[43] Sato T A,Keelan JA,Mitchell M D.Critical paracrine interactions between TNF-alpha and IL-10 renulate lipopolysaccharide-stimulated human choriodecidual cytokine and prostaglandin E2 production. J Immunol, 2003; 170(1):158.
[44] Peschon JJ, Torrance DS, Stockinn KL, et. al. TNF receptor-deficient mice reveal divernent roles for p55 and p75 in several models of inflammation. J Im-munol, 1998; 160(2):943.
[2] Morrison DK, Kaplan DR, Rapp U,eral. Signal transduction from membrane to cytoplasm growth and membrane bound oncogene products increase Raf-1phosphorylation and associated protein kinase activity. Proc Natl Acad Sci,1998;85:8855.
[3] Akcali KC,Khan SA,Moulton BC.Effect of decidualization on the expression of bax and bcl-2 in the rat uterine endometrium.Endocrinology,1998;137:3123-3131.
[4] Wang Z. Prevent from bleeding after medical abortion through prolonged application of mifepristone with misoprostol for terminating early pregnancy. Chin J Obstet Gynecol,2000;35(9):554-557.
[5]刘瑞芬,刘文琼,王玉玲.宫清方防治药物流产后阴道出血及对绒毛超微结构变化的影响[J].福建中医药,2003;34(1):12-14.
[6]栾继红.药物流产后出血副反应的防治与研究进展.湖南中医药导报,2003;9(9):43～44
[7]许梅芬,金毓翠,岑幻仙,等.药物流产后子宫刮出物的组织学观察.中华妇产科杂志,1994;29(12)739～741.
[8]房敬燕,路欣,诸定寿.药物流产后子宫刮出物的组织病理学和免疫细胞化学研究.首都医科大学学报,1999;20(2):89～91.
[9]陈兴林,陈常佩,芦劲,等.经阴道彩色多普勒对药物终止早孕子宫出血时间延长的临床观察与分析.中国超声医学杂志,1998;14(9):38～40
[10]莫凌昭.药流后阴道出血原因分析[J].华夏医学,1999;12( 2):98
[11] Spitz IM, Bardin CW. Clinical phamacology of RU486 an docrRev 1993,14:133
[12]黄丽丽,石一复,陈小端,等.米非司酮抗早孕蜕膜雌孕激素受体的免疫组织化学研究[Jl.中华妇产科杂志,1999;34(5):18-20
[13]夏革清,熊雅丽,孙永玉.米非司酮对早孕绒毛和蜕膜组织中端粒酶的影响[J]生殖医学杂志,2004;13(3):150-152
[14] Schwartzman RA,CidioWski JA Apoptosis the biochemistry and molecular biology of programmed cell death[J].En docrRev,1993;14:133
[15]何丽霞,曲陆荣,陈桂兰,等.米非司酮对人早孕蜕膜组织细胞凋亡的影响[J].生殖与避孕,1999;19(4): 216-219
[16] Welsh AO , Endoer AC.Trophoblast cell interaction and establishment blood circulation in the parictal yolk ration of the rats [J]. Anat Res,1987; 217:203
[17] Parr EL.Apoptosis as the mode of uterine epithelial celldeath during embryo implantation in mice and rats[J].Bio1 Reprod,1987; 36:211
[18]杨业洲,曹泽毅,韩宇研,等.米非司酮对人早孕绒毛细胞增殖和凋亡的影响[J].中华妇产科杂志,1998;33(5): 268-270
[19]张月莲,陈贵安,刘以训,等.正常与药物流产绒毛蜕膜组织细胞凋亡及相关基因的表达[J].中华妇产科杂志,2002;37(4): 220-222
[20]宋淑芳,宋静慧,等.米非司酮药物流产阴道出血原因探讨.内蒙古医学院学报,2006;28(3):181～184
[21]曹泽毅.中华妇产科学,北京:人民卫生出版社,2005;第2版:2852.
[22] Mirakian R,Nye K,Palazzo FF,et al. Methods for detecting apoptosis in medical abortion. J Immunol Methods,2002;265:161-175.
[23]杨雪峰,任芬若,白桦,等.米非司酮对早孕蜕膜及绒毛中雌孕激素受体的影响[J].中国实用妇科与产科杂志中,2000;16(10):605-606.
[24] Ruzycky F,Csagranda F,Audero E,et al. Differential expression of protein kinase cisoforms in the human placenta,1998;17(7):461.
[25]孙晓燕,郑岗.米非司酮对早孕绒毛组织EGFR、C-myc蛋白表达的影响[J].西安医科大学学报(医学版),2002;23(6):569-572.
[26]张玉珍.中医妇科学.北京:中国中医药出版社,2002,第一版:350-351.
[27]刘瑞芬,王丽娟.从虚热瘀论治药流后恶露不绝.山东中医杂志,2004;23(1):9～10
[28]刘文琼.中医防治药物流产后阴道出血概况.山东中医药大学学报,2001;25(1):74-76
[29]于燕,王秀霞,刘红梅,等.生化止血饮对药物流产后大鼠子宫蜕膜中FN与LM的影响[J].中国中医药科技,2004;11(4):216-7.
[30]赵瑞华.复元冲剂防治药物流产后出血的临床和实验研究[J].中国中医药科技,2004;11(4): 200- 2
[31]周幸,白世泽,李新生,等.血停灵冲剂的药效学研究[J].中国中医药科技,1997;4(5):271-272
[32]王洪萍,刘瑞芬,等.宫清颗粒治疗药物流产后阴道出血150例临床观察.中国计划生育学杂志,2005;116(6):365-367
[33]刘文琼,刘瑞芬,赵洁.宫清方防治药物流产后阴道出血临床观察.山东中医药大学学报,2003;27(1):32-36
[34]王洪萍.宫清颗粒在药物流产中作用机制探讨.中国新药与临床杂志,2007;26(1):52-55
[35]刘瑞芬,刘文琼.宫清方防治药物流产后阴道出血及对绒毛超微结构变化的影响.福建中医药,2003;34(1):12～13
[36]曹泽毅.中华妇产科学,北京:人民卫生出版社,1999;第1版:2588.
[37]上海市卫生局.妇产科诊疗常规,上海:上海科学技术出版社,1999,第1版:300.
[38]中华人民共和国卫生部.中药新药临床研究指导原则.第一辑,1993,231.
[39]沈稚琴,黄稚萍.月经血量测定的方法学和临床应用[J].陕西医学检验,1995;10(2):5-7
[40]张玉珍.中医妇科学,北京:中国中医药出版社,2002,第1版:352.
[41]张翠萍.固冲清宫汤治疗药物流产后出血过多48例.安徽中医学院学报,1994;13(1):23.
[42]卓毅.清宫逐瘀汤治疗108例米非司酮流产后阴道出血的临床观察.四川中医,1995;(1):36.
[43]吕大鸣,刘秀云.益气冲化汤治疗药流后阴道出血60例[J].中医药信息,2004;21(3): 3
[44]吴昌生.辨证治疗流产后恶露不绝113例小结.安徽中医学院学报,1991;10(2):35
[45]刘青云.中药药理学[M]北京:人民卫生出版社,1997:146-149.
[46]曲淑岩.马齿苋的药理及临床应用.吉林中医药.1985;(3):28.
[47]郑俊华.生药学[M].北京:人民卫生出版社,2002:235-240.
[48]王裕生.中药药理与应用.北京:人民卫生出版社,1983;第1版:1169.
[49]郭月芳,金祖汉,杨明华,等.宫清颗粒调经及抑菌作用研究.基层中药杂志,2001;(15)6:7-8
[50]李培植.中药益母草对小白鼠抗着床和抗早孕作用的初步研究.西安医科大学学报,1988;9(4):317.
[51]张秀成.抗生育中草药[M].北京:北京科学技术出版社,1994:72, 66, 80.
[52]宋树立.川牛膝水煎液影响小鼠妊娠的实验研究.中国医药学报,1994;9(4):40.
[53]南京药学院编.中草药学.南京:江苏科学技术出版社,1980,第1版:296.
[54]刘寿山主编.中药研究文献摘要(1962-1974).北京:科学出版社,1979:581
[55]陈振中,刘莉,李群爱,等.蒲黄的实验研究.湖南区药杂志,1984;11(2):29
[56]梁从云,王世忠,张磊,等.中药党参对异质性荧光染色的巨噬细胞功能的影响.中医药学报,1995;10(6):45
[57]王裕生主编.中药药理与应用.北京:人民卫生出版社,1983:898.
[58]李广勋.中药药理毒理与临床.天津:天津科技翻译出版公司,1992:365.
[59]郭月芳,金祖汉,杨明华,等.宫清颗粒活血祛瘀药效学研究.中成药,2002;24(8):607-609
[60] Spitz IM, Bardin CW. Clinical pharmacology of RU 486-An antiprogestin and antiglucocorticoid [J].Contraception, 1993;48: 403
[61] Vaishnaw AK,McNally JD,Elkon KB.Apoptosis in the rheumatic diseases[J]. Arthritis Rheum,1997;40;1917-1927
[62]龚非力,沈关心,李卓娅,等.医学免疫学[M] .上海科学技术出版社,2000:6.
[63]席娜.细胞凋亡与流产.四川医学,2005;26(7):803-805.
[64] Halperin R,Peller S,Rotschild M, et al. Placental apoptosis in normal and abnormal pregnancies. Gynecol Obstet Investiga,2000;50:84-87.
[65] Thiet MP, Suwanvanichkij V, Hasselblatt K, et al. Apoptosis in human term placenta. A morphological and expression study. Gynecol Obstet Investiga,2000;50:88-91.
[66] Kokawa K, Shikone T, Nakano R, et al. Apoptosis in human chorionic villi and deciduas during normal embryonic development and spontaneous abortyion in the first trimester [J].Placenta ,1998;19(1):21～26
[67] Moulton BC. Transforming growth factor stimulates endometial stromal apoptosis in witor. Endorcinology,2002;14:133-151.
[68]杨业洲,曹泽毅,韩字研等.米非司酮对人早期妊娠绒毛细胞增殖和凋亡的影响[J].医学科技,1997;1(1): 3-6
[69]刘颖,冯霞.米非司酮促进早孕绒毛及蜕膜细胞凋亡的研究[J].徐州医学院学报,2001;21(3):218～220.
[70] Anjum R,Khar A. Differential regulation of apoptosis in AK-5 tumor cells by the proto- oncogene Bcl-2: presence of Bcl-2 dependent and independent pathways. FEBS Lett, 2001;499(1-2):166-170.
[71] Shi WL,Wang JD, Fu Y, etal. The effect of RU486 on progesterone eceptor in villous and extravillous trophoblast. Hum Reprod,2001;10:953-958.
[72]席娜,刘宏伟,许良智,等.三苯氧胺联合米非司酮药物流产对早孕绒毛细胞凋亡及调控基因的影响.生殖与避孕,2005;25(11):696～699
[73]杜群,王汝俊,徐勤.活血化瘀中药对慢性萎缩性胃炎大鼠细胞增殖及凋亡的研究[J] . 2003;20(2):136-139.
[74]陈培丰.清热解毒法诱导肿瘤细胞凋亡的研究[J].浙江中医学院学报,2003;27(1):12～15.
[75]曹立幸,李泽民,李同玺.益气养血、固肾安胎法治疗肾虚流产保胎作用机理研究,2004;19(2):53～54.
[76]陈惠新,许岸高,刘集鸿.黄参方剂诱导胃癌癌前病变细胞凋亡和影响BCL-2蛋白表达的研究[J].陕西中医,2001;22(7):438-440.
[77]彭黎明,王曾礼.细胞凋亡的基础与临床[M].北京:人民卫生出版社,2000:153.
[78] Spitz IM,Bardin CW.Clinical pharmacology of RU486-An antiprogestin and antiglucocortucoid[J].Contraception,1993;48:403
[79]刘德培,查锡良,药立波,等.医学分子生物学[M].2003:528
[80]金力,沈维雄,孙志达,等.复方米非司酮对人早孕蜕膜组织雌孕激素受体的影响.生殖与避孕,2000;20:202-207.
[81]杨雪峰,任芬若,白桦,等.米非司酮对早孕蜕膜及绒毛中雌孕激素受体的影响.中国实用妇科与产科杂志,2000;16: 605-606.
[82]张立会,胡秀英,李荷莲,等.米非司酮对人蜕膜及绒毛膜雌、孕激素受体的影响.白求恩医科大学学报,1999;25: 731-732.
[83]黄丽丽,石一复,陈小瑞,等.米非司酮抗早孕蜕膜雌、孕激素受体的免疫组织化学研究.中华妇产科杂志,1999;34: 275-277.
[84]宋淑芳,宋静慧,等.米非司酮药物流产阴道出血原因探讨.内蒙古医学院学报2006;28(3):181～184
[85] Mirakian R,Nye K,Palazzo FF,et al. Methods for detecting apoptosis in medical abortion.J Immunol Methods,2002;265:161-175.
[86] zaytseva ts, goncharova vn, morozova ms, et al. the effect of ru486 on progesterone and oestrogen receptor concentrations in human decidua on early pregnancy. hum reprod, 1993;8:1288-1292.
[87] hill ncw, rivera j, bernal al, et al. the effect of ru486 on progesterone and oestrogen receptor concentrations in the decidua and placenta in early pregnancy. hum reprod, 1990;5:464-467.
[88]曹泽毅.中华妇产科学,北京:人民卫生出版社,2005,第2版:2852.
[89]王宏.国外医学免疫学分册,1995,3:146-148.
[90] Murray JF,Dowing JA,Evans c et al.J Endocrinol,1993;137(2):253-264
[91] Orwitz ER, Robinson JN,Repke JT.Ihe initiation of parturition: A comparative analysis Across the species. Curr Probl Obstet Gynecol Fertil, 1999;22: 46-71.
[92]张丽凤,苏应宽,盖凌,等.表皮生长因子受体在子宫内膜、早孕蜕膜及滋养细胞中的表达[J].中华妇产科杂志,1999;34(6):357-359.
[93] Piva M, Flieger,O Rider V. Growth factor control of cultured rat uterine stromal cell proliferation is progesterone dependent[J].Bio Reprod, 1996;55(6):1333-1342.
[94] Eldadah BA, Faden AI. Caspase pathways, neuronal apoptosis, and CNS injury. J Neurotrauma,2000;17(10):811-829.
[95] Zhang X M .The focuses in the researches of apoptosis[J].Chin J Pharmacol Toxicol(中国药理学与毒理学杂志),2000;14(2):81-85.
[96] Raff M.Cell suicide for beginners[J].Nature,1998;396(6707):119-122
[97] Kumar S. The apoptotic cysteine protease CPP32.Int J Biochem Cell, 1997;29 (3):393-396.
[98] Enari M,Sakahira H,Yokoyama H,et al.A caspase activated DNase that degrades DNA during apoptosis,and its inhibiter ICAD[J].Nature,1998;391(6662):43-50.
[99] Slee EA, Keogh SA, Martin SJ.Cleavage of BID during cytotoxic drug and UV radiation-induced apoptosis occurs downstream of the point of Bcl-2 action and iscatalysed by caspase-3:a potential feed-back loop for amplification of apoptosis-assciated[J].Cell Death Differ,2000;7(6): 556-565.
[100] Huppertz B, Frank HG, Reister F, et al.Apoptosis cascade progr- esses during turnover of human trophoblast:analysis of villous cytotropho- blast and syncytial fragments in vitro.Lab Invest,1999;79(12):1687-1702.
[101] ThornberryNA, LazebnikY.Caspases: Enemieswithin[J].Science,1998; 281 (8): 1312-1316.
[102] Wallach D. Suicide by order:some open questions about the cell killing activities of the TNF ligand and receptor family.Cytokine Growth Factor Reviews ,1996; 7(3):211～221.
[103] Luo X, Budihardjo I, Zou H, et al. Bid, a Bcl-2 interacting protein, mediates cytochrome release in response to activation of cell surface death receptors . Cell,1998;94(4):481-490.
[104] Li H, Zhu H, Xu CJ,et al.Cleavage of BID by Caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell, 1998; 94:491-501.
[105] Li H,Yan J.Deciphering the pathways of life and death.Curr Opin Cell Biol, 1999;11:261-266.
[106] Schulze Osthoff K, Ferrari D, Los M, et al.Apoptpsis signaling by death eceptors.Eur J Biochem, 1998;254:439-459.
[107] Heiskanen KM, Bhat MB HW, et a1.Mitochondrial depolarization accompanies cytochrome c release during apoptosis in PC6 cells. JBiol Chem, 1999;274: 5654-5658.
[1]蒋惠贞.活血化瘀法对药物流产后HCG水平下降伴出血不止的疗效观察[J] .新中医,1995;27(9):24.
[2]胡洪瑞.固经灵治疗药物流产后出血30例[J] .新中医,1996; 23 (2):20.
[3]卞宜心.宫清方治疗药物流产后出血过多127例[J].浙江中医杂, 1996; 31(7): 299.
[4]王学瑞.中药治疗药物流产出血的疗效观察[J].中医杂志,1993;34(8):491.
[5]吕大鸣,刘秀云.益气冲化汤治疗药流后阴道出血60例.中医药信息,2004; 21(3): 3.
[6]王淑善、王少华.用消补兼施法治药流后恶露不止的经验.辽宁中医杂志, 1999; (10)436-8.
[7]张婷婷.中药祛膜肠治疗药物流产后出血214例临床与实研究.中国中西医结合杂志,1997;(9)534-6.
[8]何晓虹.生化汤治疗药物流产后恶露不绝197例观察.时珍国医国药,2001;(9): 828.
[9]孙建新,王玲.辨证论治药流后出血.甘肃中医,2002;15(6):63-4.
[10]王佩.药物流产后阴道出血的中医辨证治疗.甘肃中医学院学报,2003;20(2): 24-5.
[11]王桐生,彭珊英,龙子江.药物流产后出血的中药治疗研究近况.承德医学院学报, 2001;18(2):160-3.
[12]梁晶.药物流产后诸证的中医辨证.四川中医药学报,1997;15(2):29.
[13]王桂芳.化瘀清宫汤治疗药物流产后出血180例[J].实用中医药杂志,2001;17(4):12.
[14]叶铤.生化逐瘀汤防治药物流产后出血的临床观察[J].现代中西医结合杂志,2004;13(8) : 16.
[15]马淑秀.参芪生化汤加味药流后阴道流血Go[J].辽宁中医杂志.1998;25(2): 73.
[16]刘志芬.益气清宫汤治疗药流后出血不止[J].四川中医,1998;16(2):42.
[17]刘凤英.芪蒲坤舌汤治疗药物流产后恶露不绝31例[J].广西中医药,1994;17(4):I 5.
[18]杨景海.参芪当坤汤治疗药物流产后阴道出血29例[J].光明中医杂志,1997;(3):29.
[19]应苹.芩酱缩宫汤缩短药物流产后阴道出血时间160例临床观察[J].中医杂志,1999;40(2):22.
[20]谢鸣.中药辅助米非司酮终止早孕的疗效观察[J].中华妇产科杂志,1996;31(6):373.
[21]张琼芳.清宫止血饮治疗药物及入工流产后出血[J].中国医药学报,1995;10(6):29.
[22]王佩期.固阴煎治疗药物流产后顽固性子宫出血34例[J].实用中医药杂志, 1998;5(14):5.
[23]戴雨红.固冲汤治疗药物流产后持续出血89例.实用中药杂志[J],1999;15(8):34.
[24]张琼,薛赛琴,姜坤.宫腹康胶囊治疗药物流产术后子宫出血的临床研究[J].中药新药与临床药,2001;12(5):318-320
[25]石礼红,张宏丽,李静芳.四物合剂治疗药流后出血[J].江西医学院学报,2002; 42(1):116.
[26]郭小莺.妇血康治疗药物流产后出血100例[J].福建中医药,2001;32(2): 48-9.
[27]冷观群.益母片治疗药物流产后阴道出血98例疗效分析[J].中国中医急症,2001;10(2):28.
[28]孙磊.云南白药减少药物流产后出血80例分析[J].中国计划生育学杂志,1999;7(4):173.
[29]李国辉.自拟妇乐散外敷治疗药物流产后持续出血25例临床观察[J].中医外治杂志,1999;6(3):17.
[30]潘秀群,陈济民.中药内服加外用治疗药物流产后出血不止124例[J].吉林中医药,1999;19(3) : 33- 34.
[31]赵荣胜,等.产乐冲剂减轻药物流产后出血的临床与实验研究[J].中国计划生育学杂志,1998; (3):108-111.
[32]严福生,谢小云,黄晓翘,等.清宫汤协助药物流产的临床与实验研究[J].安徽中医学院学报,2003;22(5)23-26.
[33]王晓东,赵军宁,张自嘉,等.宫复安对子宫的药理作用研究[J].中药药理与临床,1999;15(1):33.
[34]于燕,王秀霞,刘红梅,等.生化止血饮对药物流产后人鼠子宫蜕膜中FN与LM的影响[J].中国中医药科技,2004;11(4): 216-7.
[1] Vaishnaw AK, McNally JD, Elkon KB .Apoptosis in the rheumatic diseases [J].Arthritis Rheum,1997;40:1917-1927.
[2]李翠兰,胡章和,曹来英,等.正常妊娠中细胞增殖细凋亡情况的研究[J].中国实用妇科和产科杂志,2001;6(4):223～224.
[3] Smith SC, Bakcr PN, Symonds EM .Plaental apoptosis in normal human pregnancy[J].AmJ Obstet Gynaecol,1997;177(1):57- 65.
[4] Kokawa K, Shikone T, Nakano R, et al.Apoptosis in human chorionic villi and deciduas during normal embryonic development and spontaneous abortyion in the first trimester[J].Placenta ,1998;19(1):21～26.
[5]杨业洲,曹泽毅,韩字研,等.米非司酮对人早期妊娠绒毛细胞增殖和凋亡的影响[J].医学科技,1997;1(1): 3-6.
[6]刘颖,冯霞.米非司酮促进早孕绒毛及蜕膜细胞凋亡的研究[J].徐州医学院学报,2001;21(3):218～220.
[7] SMITH S C,BAKER P N,SYMONDS E M.Placental apoptosis in normal human pregnancy[J].Am J ObsterGynecol,1997;177:57.
[8]刘德培,查锡良,药立波,等.医学分子生物学[M].2003:528.
[9]丁峰,傅国强,邢福棋,等.米非司酮对人早孕期蜕膜细胞凋亡及其调控基因bcl- 2/bax的影响[J].现代妇产科进展,2002;11(1): 36- 38.
[10]高红军,代解杰等,Bax/Bcl-2mRNA在恒河猴药物流产胎盘中的表达.生物技术,2005;15(2):21-24.
[11] Cheng EHY,David G,Kirsch,et al.Conversion of Bcl-2 to a bax-like death dffector by caspases[J].Science,1997;278(5354):1966-1968.
[12] Raff M.Cell suicide for beginners[J].Nature,1998;396(6707):119-122.
[13] Enari M,Sakahira H,Yokoyama H,et al.A caspase activated Dnase that degrades DNA during apoptosis ,and its inhibiter ICAD[J]. Nature, 1998;391(6662):43-50.
[14] Slee EA, Keogh SA, Martin SJ.Cleavage of BID during cytotoxic drug and UV radiation-induced apoptosis occurs downstream of the point of Bcl-2 action and is catalysed by caspase-3:a potential feed-back loop for amplification of apoptosis-assciated[J].Cell Death Differ, 2000; 7(6): 556-565.
[15]唐旭东,周客元,蔡康荣.高三尖杉脂碱通过激活caspase-3诱导鼻咽癌细胞凋亡[J].细胞与分子免疫学杂志,2002;18(4):366-368.
[16]杜红俊,惠延年,王雨生,等.caspase-3在柔红霉素诱导的人视网膜色素上皮凋亡中的作用[J].第四军医人学学报,2001;22(7):609-611.
[17]李刚,陈必良,米非司酮对早孕绒毛滋养层细胞Bcl-2和caspase-3表达的影响.ISSN 1007-8738细胞与分子兔疫学杂志(Chin.J Cell Mol Immunol) 2003;19(2):136-137.
[18] Wallach D. Suicide by order:some open questions about the cell killing activities of the TNF ligand and receptor family.Cytokine Growth Factor Reviews, 1996;7(3):211～221.
[19] Luo X, Budihardjo I, Zou H, et al. Bid, a Bcl-2 interacting protein, mediates cytochrome release in response toactivation of cell surface death receptors .Cell,1998;94(4):481-490.
[20] Li H, Zhu H, Xu CJ,et al.Cleavage of BID by Caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis.Cell,1998,94: 491-501.
[21] Schulze Osthoff K,Ferrari D,Los M,et al. Apoptosis signaling by death receptors.Eur J Biochem, 1998;254: 439-459i.
[22]周春,董迪荣等.诊断超声照射对人早孕绒毛细胞Caspase 3,8蛋白表达的影响.中国超声医学杂志,2005;21(4):256-258.
[23] Medena JP,Scaffidi C,Kischkel ME,et al.FLICE is activated by association with the CD95 death-inducing signaling complex [J].EMBO J,1997;16:2794.
[24] Hammer A, Blaschitz A,Daxbock C,et al .Fas and Fas-ligand are expressed in the utero placental unit of first-trimester pregnancy[J].AmJReprod Immunol,1999; 41(1):41～45.
[25]杨业洲,韩字研,曹泽毅,等.米非司酮对人早期妊娠绒毛ICE、Fas表达的影响[J].华西医大学报,1998;29(2):216- 219.
[26] Ejima K, Koji, Tsuruta D,et al.Induction of apoptosis inplacentas of pregnant mice exposed to lipopolysacharides: possible invovement of Fas/Fas ligand system[J].Biol reprod, 2000;62(1):178-185.
[27]张月莲,陈贵安等.正常与药物流产绒毛蜕膜组织细胞调亡及相关基因的表达[J].中华妇产科杂志,2002;37(4):220-223.
[28] Moore ED,Ring M,Scriven DR, et al. The role of protein kinase Cisozymes in bombesin-stimulated gastrin rlease from human antral gastrin cells J Biol Chem,1999;274:22493.
[29] Heagerty .AM,Ollerenshaw JD. The phosphoinositide signaling system and hypertension.J Hypertens,1987;5:51.
[30] Stariha RL,Kim SU.Protein kianse C and mitngenantivated protein kinase signaling in oligodendrocytes. Microse Res Tech,2001;52:680.
[31]赖仁胜,周溶等.米非司酮影响早孕滋养细胞的信号传导和凋亡的机制研究.中国实用妇科与产科杂志,2000;16(10)599-601.
[32]朱瑾,周剑萍.c-myc基因mRNA在小鼠胚胎着床期间的表达.生殖与避孕,2001;21(2):77-81.
[33] Pfeifer-Ohlsson S, Goustin AS, Rydnert J, et al. Spatial and temporal pattern of cellular myc onconene expression in developing human placenta: implications for embryonic cell proliferation. Cell, 1984;38: 585-596.
[34] Orwitz ER, Robinson JN, Repke JT.Ihe initiation of parturition: A comparative analysis Across the species. Curr Probl Obstet Gynecol Fertil, 1999,;22: 46-71.
[35] MaruoT,MatsuoH,OtaniT,etal:Role of epidermal growth factor and its receptor in the development of human placenta. Reprod Fertil Dev, 1995; 7(6):1465-1470.
[36]张丽凤,苏应宽,盖凌,等.表皮生长因子受体在子宫内膜、早孕蜕膜及滋养细胞中的表达[J].中华妇产科杂志,1999;34(6):357-359.
[37]付小锁,张景艳.表皮生长因子对人早孕滋养层细胞孕酮分泌的影响.锦州医学院学报,2002;23(2)13～15.
[38]张晶,夏思菊,张建国.米非司酮对早孕蜕膜肿瘤坏死因子-α及转化生长因子-β表达的影响[J].中华妇产科杂志,2001;36 (1): 27-29.
[39] Feinberg RF, Kliman H.I Wang CL Transfoming growth factorbeta stimulates trophoblast oncofetal fibronectin synthesis in vitra implicalions for trophoblast implantation in viVo[J].J Clin Endocrinol Metab, 1994;78( 5): 1241-1248.
[40]金莉萍,邵敬於,李大金,等.米非司酮对早孕蜕膜与绒毛转化生长因子-β基因表达及血清肿瘤坏死因子-α的影响[J].生殖与避孕,2003;23(1):26- 30.
[41]刘纹琰,刘延,刘晓瑗.上海交通大学学报(医学版).早孕药物流产绒毛和蜕膜组织TGF-β1的表达,2006;26(12):1365-1368.
[42] Okuda K,Sakumoto R. Multiple roles of TNF super family members in corpus luteum function .Reprod Biol Endoc, 2003; 10(1):95.
[43] Sato T A,Keelan JA,Mitchell M D.Critical paracrine interactions between TNF-alpha and IL-10 renulate lipopolysaccharide-stimulated human choriodecidual cytokine and prostaglandin E2 production. J Immunol, 2003; 170(1):158.
[44] Peschon JJ, Torrance DS, Stockinn KL, et. al. TNF receptor-deficient mice reveal divernent roles for p55 and p75 in several models of inflammation. J Im-munol, 1998; 160(2):943.