MMP-2、TIMP-2及VEGF蛋白在子宫内膜异位症裸鼠模型组织中的表达及意义

THE EXPRESSION OF MATRIX METALLOPROTEINASE 2,TISSUE INHIBITOR OF METALLOPROTEINASE 2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR IN NUDE MOUSE ENDOMETRIOSIS MODEL

目的建立裸鼠子宫内膜异位症(EMs)模型,检测基质金属蛋白酶-2(MMP-2)、金属蛋白酶组织抑制因子-2(TIMP-2)、血管内皮生长因子(VEGF)在异位内膜及正常内膜的表达,探讨其在EMs发生、发展中的作用。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,光镜下观察异位病灶的形态学特点,并采用免疫组化方法(PV-6001/6002法)检测异位内膜MMP-2、TIMP-2、VEGF蛋白表达水平,与种植前子宫内膜比较。结果光镜下观察,异位病灶具有增生期特点;且异位内膜较正常内膜MMP-2/TIMP-2比值增高(t=12.919,P<0.01),VEGF蛋白表达增强(t=2.647,P<0.05)。结论裸鼠模型是EMs早期临床研究的理想模型;MMP-2/TIMP-2比值升高及VEGF表达增强与异位内膜的高侵袭性和高血管新生能力有关,在EMs的发生发展中起重要作用。

Objective Based on the constructed model of nude mouse endometriosis, to detect the expression of matrix metalloproteinase 2 （MMP-2）, tissue inhibitor of metalloproteinase 2 （TIMP-2） and vascular endothelial growth factor （VEGF） in the ectopic endometrial tissues and discuss the role of them in the pathogenesis of endometriosis. Methods The model was constructed by injecting endometrial chipping at late secretory satge of child-bearing age woman into the peritoneal cavity of experimental animals killed at 18 d after the injection. The expressions of MMP-2, TIMP-2 and VEGF in the grafts were detected by immunohistochemical method. Results The characteristics of proliferative stage were observed in ectopic focus, the ratio of endometrial MMP-2/TIMP-2 was higher, and VEGF expression enhanced. Conclusion The nude mouse model is an ideal model for the study of early phase of endometriosis. The increase of MMP-2/TIMP-2 ratio and VEGF expression are related to high invasion and angiogenesis of endometriosis, which plays an important role in the occurrence and development of the disease.