MMP-2/TIMP-2在人及裸鼠异位子宫内膜组织中的表达及与雌、孕激素的关系  

Expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in human and nude mice ectopic endometrium and the effect of estrogen and progestin on their expressions

作　　者：娄艳辉[1] 夏玉芳[1] 李全香 郭新华[1] 

机构地区：[1]青岛大学医学院附属医院妇科,青岛266003 [2]东营市人民医院妇产科

出　　处：《现代妇产科进展》2009年第7期531-536,共6页Progress in Obstetrics and Gynecology

基　　金：山东省自然科学基金资助项目(No:Y2003C01)

摘　　要：目的:探讨MMP-2/TIMP-2在子宫内膜异位症发病机制中的作用及雌、孕激素对二者表达的影响。方法:(1)用RT-PCR及SP免疫组化法检测51例异位内膜组织及28例正常子宫内膜组织中MMP-2/TIMP-2mRNA及蛋白的表达;(2)建立裸鼠子宫内膜异位症模型并予以雌、孕激素干扰,随机分成4组(E组、P组、E+P组及对照组C),观察不同激素干扰下裸鼠内异症模型的种植成功率及其大体、镜下的形态表现;用免疫组化法检测MMP-2/TIMP-2蛋白在不同组别裸鼠异位内膜中的表达。结果:(1)四组裸鼠内异症模型中种植物均成活,总种植成功率86.4%(51/59),各组间成功率无显著差异。其中P组种植物数量较其他组明显增多,P组、E+P组种植物明显大于E组、C组。受外源性雌、孕激素影响,镜下种植物分别呈现增生期和分泌期特点;(2)MMP-2/TIMP-2mRNA及蛋白在人及各组裸鼠异位内膜组织中均有表达,MMP-2相对表达量明显高于正常子宫内膜,差异有统计学意义(P<0.05);TIMP-2表达与正常内膜组织则无显著差异,MMP-2/TIMP-2比值明显增高(P均<0.01)。(3)E组、E+P组MMP-2蛋白表达均明显高于C组,而P组与C组无差异;TIMP-2蛋白在C组的表达明显高于其他激素干扰组。结论:裸鼠模型是EMs早期临床研究的理想模型。MMP-2/TIMP-2在人及裸鼠异位组织中异常表达,动态平衡紊乱,在EMs发生发展中起重要作用。雌激素可上调MMP-2蛋白表达,促进异位内膜种植;孕激素未表现对抗雌激素的作用,且通过抑制TIMP-2表达,同样造成MMP-2/TIMP-2比值升高,使异位内膜侵袭性增高,表现出"孕激素抵抗"现象。Objective ： To observe the roles of matrix metalloproteinase2 （MMP-2） and tissue inhibitor of metalloproteinase2 （TIMP-2） in the pamogenesls of enuomemosis and the effects of estrogen and progestin on their expressions. Methods： Immunohistochemical S-P method and RT-PCR were employed to detect the expression of MMP-2 and TIMP-2 in the ectopic tissues of 51 patients with endometriosis and 28 normal controls. 59 nude mice were injected with human late secretory phase endometrial chipping and then were randomly devided into 4 groups treated with estrogen, progestin, estrogen combined with progestin and saline as control group. The implantation rates, morphological traits of the grafts was observed and the expressions of MMP-2 and TIMP-2 detected by immunohistochemistry method in the grafts obtained from different groups after the mice were killed. Results：Typical endometrial glands and stroma were observed in all groups, and among which the implantation rates were similar. The administration of progestin supplementation in vivo was associated with muhiple peritoneal implantation sites and with significantly larger implants. The transplanted endometria showed proliferative or secretory changes coincident with estrogen or progestin administration. The expression of MMP-2 was higher and the expression of TIMP-2 was lower in human and nude mice ectopic endometria than in normal endometria and the ratio of MMP-2/TIMP-2 increased （ P 〈 0.05, P 〈 0.01 ）. The expression of MMP-2 was higher in estrogen and estrogen-progestin group than in control group and the expression of TIMP-2 was lower in all the three treated groups than in control group. Conclusion： The nude mouse is an appropriate model to study the response of early-stage ectopic endometrium to sex steroid. Progestrin can not inhibit the expression of MMP-2 and the effect of estrogen on ectopic endometrium,which is called ＂progestin resistance＂. The high expression of MMP-2 and the low expression of TIMP-2 in ectopic endometrial tissue ma

关 键 词：子宫内膜异位症 小鼠 裸 疾病模型 动物 基质金属蛋白酶-2 金属蛋白酶2组织抑制剂 雌激素 孕激素 

分 类 号：R711.71[医药卫生—妇产科学]