外源性雌、孕激素对裸鼠人子宫内膜异位症病灶中MMP-2、TIMP-2及VEGF蛋白表达的影响

Effect of Estrogen and Progestin on Expression of Matrix Metalloproteinase-2,Tissue Inhibitor of Metalloproteinase-2 and Vascular Endothelial Growth Factor in Nude Mouse Endometriosis Mode

目的:探讨雌、孕激素对异位内膜及MMP-2、TIMP-2、VEGF蛋白表达的影响。方法:将育龄妇女正常分泌晚期子宫内膜注入裸鼠盆腹腔,建立EMs裸鼠模型,随机分为四组,分别予雌激素(E)、孕激素(P)、雌激素+孕激素(E+P)及对照(C)组生理盐水肌肉注射。术后18天处死裸鼠,取异位组织,采用免疫组化方法(PV6001/6002法)检测各组异位内膜MMP-2、TIMP-2、VEGF蛋白表达水平,与种植前子宫内膜比较。结果:异位内膜较正常内膜MMP-2、VEGF蛋白表达增强,TIMP-2蛋白表达减弱(P均<0.01);E组、P组、E+P组MMP-2/TIMP-2比值及VEGF蛋白表达均高于C组(P均<0.01),E+P组同E组相比MMP-2/TIMP-2比值及VEGF蛋白表达无差别(P均>0.05)。结论:异位内膜的侵袭性和血管新生能力增强,且对激素的反应不同于正常内膜。

Objective：To investigate the effect of estrogen and progestin on the expression of MMP-2, TIMP-2 and VEGF in ectopic endometrium. Methods：60 nu/nu mice were injected with the late secretory endometrial chipping and then were randomly divided into 4 groups： one group were injected with estrogen, one group with progestin, one group with estrogen and progestin, and the control group with sodium chloride. The mice were killed on d18 and the grafts were obtained. The expressions of MMP-2, TIMP-2 and VEGF in the grafts and normal endometrium were detected by immunohistochemistry. Results：Typical endometrial glands and stroma were observed in all groups. The expression of MMP-2 and VEGF were increased and the expression of TIMP-2 were decreased. Estrogen or progestin could enhance the ratio of MMP-2/TIMP-2 and the expression of VEGF. However, progestin couldn＇t antagonize the effect of estrogen on the expression of MMP-2 and VEGF. Conclusion：The ectopic endometrium has enhanced the ability of invasion and angiogenesis and the reaction to hormone were different from normal endometrium.