【作者】 张俊勤；

【导师】 闫萍；

【作者基本信息】 河北医科大学 ， 妇产科学， 2008， 硕士

【摘要】 目的:本实验从米非司酮终止早孕的作用机制出发,研究正常早期妊娠、顿服150mg米非司酮12h、24h、48h后对人早孕蜕膜、绒毛组织超微结构及基质金属蛋白酶系统(MMPs)中基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制因子-1(TIMP-1)表达的影响,比较其不同作用时间对早孕蜕膜、绒毛组织的作用有无差别,为临床缩短药物流产时间,简化药物流产方案提供理论基础。方法:将80例妊娠49天以内的妇女,随机分为4组,即对照组、用药12h组、24h组、48h组,每组20例;对照组:采用常规负压吸引术终止妊娠。服药组分别一次性口服米非司酮150mg,12h、24h、48h后行负压吸引术。收集各组所得蜕膜、绒毛组织,分别应用光镜、透射电子显微镜观察各组早孕蜕膜、绒毛组织细胞形态结构的改变;同时应用免疫组织化学S-P法检测MMP-2、MMP-9、TIMP-1在各组早孕蜕膜、绒毛组织中的表达情况。运用SPSS(13.0)软件包进行统计学分析。结果:1超微结构结果:在米非司酮的作用下,蜕膜、绒毛细胞超微结构的改变主要表现在大蜕膜细胞皱缩,粗面内质网(RER)和线粒体(Mi)肿胀,颗粒细胞中高电子密度颗粒减少或消失;合体滋养细胞则表现不同程度的退行性改变,细胞滋养细胞仅出现轻度改变。蜕膜、绒毛细胞超微结构受损程度的比较,各服药组均高于对照组(P<0.05),而各用药组之间均无统计学意义(P>0.05)。2免疫组化结果:MMP-2、MMP-9、TIMP-1均为胞浆表达,在蜕膜细胞、腺上皮细胞、腔上皮细胞、细胞滋养细胞、合体滋养细胞的胞浆、胞膜均有强烈的表达。蜕膜组织中,MMP-2在对照组、口服米非司酮12h组、24h组、48h组的阳性目标平均光密度值分别为0.1555±0.0079、0.1952±0.0072、0.1958±0.0010、0.1967±0.0069 ,在绒毛组织分别为0.1555±0.0083、0.2033±0.0059、0.2076±0.0092、0.2079±0.0088,用药组在蜕膜和绒毛组织的表达均高于对照组(P<0.05),而各用药组之间均无统计学意义(P>0.05)。MMP-9在四组蜕膜组织的阳性目标平均光密度值分别为0.1656±0.0056、0.2032±0.0067、0.2051±0.0070、0.2084±0.0078 ,在绒毛组织分别为0.1617±0.0047、0.2025±0.0074、0.2039±0.0095、0.2099±0.0113,用药组在蜕膜和绒毛组织的表达均高于对照组(P<0.05),而各用药组之间均无统计学意义(P>0.05)。TIMP-1在四组蜕膜组织的阳性目标平均光密度值分别为0.1679±0.0127、0.1382±0.0071、0.1402±0.0102、0.1355±0.0077 ,在绒毛组织分别为0.1548±0.0098、0.1349±0.0106、0.1349±0.0093、0.1273±0.0095,用药组在蜕膜和绒毛组织的表达均低于对照组(P<0.05),而各用药组之间均无统计学意义(P>0.05)。蜕膜组织中MMP-9/TIMP-1的比值在四组中分别为0.9914±0.0837、1.4493±0.1369、1.4950±0.1352、1.5182±0.0884 ,在绒毛组织分别为0.9937±0.05534、1.5216±0.1066、1.5138±0.1405、1.5994±0.0842,其比值在用药组蜕膜和绒毛组织中均高于对照组(P<0.05),而各用药组之间均无统计学意义(P>0.05)。结论:1说明了米非司酮使大蜕膜细胞蛋白合成受阻,颗粒细胞释放松弛素,基质网状纤维溶解,内膜剥脱,滋养细胞失去支持,血供不足,引发流产。2 MMP-2、MMP-9在药物流产的蜕膜、绒毛组织中的表达水平显著高于正常妊娠,TIMP-1的表达显著降低,而MMP-9/ TIMP-1的比值显著升高,证实了三者在早期妊娠药物流产发生过程中具有重要作用,MMP-9和TIMP-1的平衡对于正常早期妊娠的维持起重要作用。3本课题通过比较米非司酮不同作用时间对蜕膜、绒毛组织形态结构及MMPs表达的影响,揭示了顿服150mg米非司酮12h、24h对蜕膜、绒毛组织的抑制作用与48h时相似,此时应用米索前列醇的流产效果在理论上具有可行性,药物流产两种药物的用药间隔最早可以缩短到12h。更多还原

【Abstract】 Objective: This study of mifepristone from terminating the mechanism in early pregnancy, researching the influence of mifepristone on the ultrastructure and the expression of MMP-2、MMP-9、TIMP-1 of human decidua and villus in early pregnancy by swallowing mifepristone 150 mg at one time respectively affect on 12h、24h、48h, to compare whether different treatment time of mifepristone existing distinction of decidua and villus in early pregnancy, so that a theoretical basis for shortening the time and simplifying the schedule of clinical medical abortion might be provided.Methods: 80 cases pregnant women within 49 days, were randomly divided into four groups: control group, medication 12 h group, 24 h group, 48 h group, and 20 cases each of .The pregnant women in the control group were terminated of pregnancy by conventional suction. The medication groups swallowed mifepristone 150 mg at one time, 12h、24h and 48h later, suction was operated, and the decidua and villus were taken as soon as possible. Specimens were observed by light microscope and transmission electron microscopy. The expression of MMP-2、MMP-9、TIMP-1 were detected in decidua and villus by immunohistochemistry(SP). All data were analysed by SPSS(13.0) for Windows.Results:1 Ultrastructural resultsOn the role of mifepristone, the variance of decidua and villus on the ultrastructure mainly appearance that large decidual cell shrinkage, rough endoplasm reticulum and mitochondria swell;and electron dense particles in the decidual granular cells decrease or disappear; villous syneytiotrophoblast which have active function show various degrees of degenerative changes,and langhans cell only change slightly. As for the damaged degree of decidua and villus on the ultrastructure, the treated group exceed the control group remarkably (P <0.05), and among the treated groups there are no significant difference (P> 0.05).2 Immunohistochemical results: All of MMP-2、MMP-9、TIMP-1 express strongly in the cytoplasm of decidual cells、glandular epithelial cells、cavitary epithelial cells、cytotrophoblast and syncytiotrophoblast cells、capillary endothelial cells of each group.In decidua, the positive goal of the average optical density values of MMP-2 are respectively 0.1555±0.0079、0.1952±0.0072、0.1958±0.0010、0.1967±0.0069 in the control group, taking mifepristone 12 h group, 24 h group, 48 h group, and they are respectively 0.1555±0.0083、0.2033±0.0059、 0.2076±0.0092、0.2079±0.0088 in villus , the treated groups is higher than the control group(P<0.05), and among the treated groups there are no statistical significance (P> 0.05).The positive goal of the average optical density values of MMP-9 in decidua are respectively 0.1656±0.0056、0.2032±0.0067、0.2051±0.0070、0.2084±0.0078 in the four groups, and they are respectively 0.1617±0.0047、0.2025±0.0074、0.2039±0.0095、0.2099±0.0113 in villus , the treated groups is higher than the control group(P<0.05), and among the treated groups there are no statistical significance (P> 0.05).The positive goal of the average optical density values of TIMP-1 in decidua are respectively 0.1679±0.0127、0.1382±0.0071、0.1402±0.0102、0.1355±0.0077 in the four groups, and they are respectively 0.1548±0.0098、0.1349±0.0106、0.1349±0.0093、0.1273±0.0095 in villus , the treated groups is higher than the control group(P<0.05), and among the treated groups there are no statistical significance (P> 0.05).The proportionality of MMP-9/TIMP-1 in the villus and decidua of the taking mifepristone groups are higher than the control group(P<0.05). The expression of MMP-9/TIMP-1 in the decidua of the four groups are respectively 0.9914±0.0837、1.4493±0.1369、1.4950±0.1352、1.5182±0.0884, and in the villus are respectively 0.9937±0.0554、1.5216±0.1066、1.5138±0.1405、1.5994±0.0842, and among the treated groups there are no statistical significance (P> 0.05).Conclusion:1 This study explaine that mifepristone cause the decidual cells protein synthesis blocked, granule cells released relaxin, reticular fiber of matrix dissolved, endomembrane exfoliated, trophoblast cells lost support, blood supply inadequated, triggered abortion.2 The expression of MMP-2、MMP-9 in decidua and villus of the taking mifepristone groups are all higher than the control group, and the expression of TIMP-1 is lower than the control group, the proportionality of MMP-9/TIMP-1 are higher significantly, all of which explain MMP-2、MMP-9 and TIMP-1 play an important role in the process of medical abortion in early pregnancy,MMP-9 and TIMP-1 for the balance of the maintenance of normal early pregnancy play an important role.3 This study research the influence of mifepristone on the ultrastructure and the expression of MMP-2、MMP-9、TIMP-1 of human decidua and villus in early pregnancy, reveal that swallowing mifepristone 150 mg at one time 12h or 24h, the inhibitory action of decidua and villus is as similar as 48h, if misoprostol used at this time, the effect of abortion might be comparable in theory with the traditional treatment for the standard programme of 48 h interval, so that the interval of the two drugs for medical abortion might be shortened to 12 h.更多还原