放置宫内节育器对子宫内膜血管内皮生长因子及其激酶受体表达及微血管密度变化的影响

目的探讨放置固定式带铜宫内节育器(FCu-IUD)和含吲哚美辛FCu-IUD(FICu-IUD),对子宫内膜组织中血管内皮生长因子(VEGF)及其激酶受体(KDR)表达以及微血管密度(MVD)变化的影响及意义.方法采用免疫组化法及原位杂交法,检测放置FCu-IUD妇女(10例,FCu-IUD组)及放置FICu-IUD妇女(10例,FICu-IUD组)放置IUD前后子宫内膜VEGF、VEGF mRNA及KDR的表达,并计数子宫内膜MVD.结果 FCu-IUD组放置IUD后,VEGF及KDR蛋白为0.568±0.027,0.244±0.022,均高于放置IUD前的0.357±0.032,0.215±0.029,放置IUD前后比较,差异有显著性(P<0.05).FCu-IUD组放置IUD前VEGF mRNA表达为0.359±0.022,低于放置IUD后的0.425±0.019,放置IUD前后比较,差异有显著性(P<0.05).FICu-IUD组放置IUD前后VEGF、KDR蛋白及VEGF mRNA表达比较,差异无显著性(P>0.05). FCu-IUD组放置IUD后MVD为19.8±4.8,明显高于放置IUD前的15.4±2.8,且与VEGF蛋白的表达呈正相关关系(r=0.847,P<0.01).FICu-IUD组放置IUD前后MVD比较,差异无明显性(P>0.05).结论放置FCu-IUD可促进子宫内膜VEGF及KDR的表达,FICu-IUD可抑制子宫内膜VEGF及KDR的生成.VEGF及KDR可能参与了FCu-IUD 及FICu-IUD所引起的子宫内膜微血管结构和功能的改变.

Effects of intrauterine contraceptive device on expression of vascular endothelial growth factor, kinase insert domain-containing receptor and microvessel density in endometrium

OBJECTIVE: To investigate the expression of vascular endothelial growth factor (VEGF) and its receptor, kinase insert domain-containing receptor(KDR) and microvessel density (MVD) in endometrium from women wearing fixed copper-intrauterine contraceptive device (IUD, FCu-IUD) or fixed indomethacin-releasing copper-IUD (FICu-IUD). METHODS: Twenty healthy women were divided into two study groups: 10 cases wearing the FCu-IUD (FCu-IUD group), 10 cases wearing the FICu-IUD (FICu-IUD group). Immunohistochemical technique was used to determine the expression of VEGF and KDR in endometrium, and the microvessel density (MVD) was counted. The expression of VEGF mRNA was determined by in situ-hybridization. RESULTS: Before insertion of FCu-IUD, the expression of VEGF and KDR proteins was 0.357 +/- 0.032 and 0.215 +/- 0.029 respectively. After insertion of FCu-IUD, the expression of VEGF and KDR proteins was 0.568 +/- 0.027 and 0.244 +/- 0.022 respectively, significantly higher than before insertion (P < 0.05). The expression of VEGF mRNA was 0.359 +/- 0.022 before insertion of FCu-IUD, after insertion of FCu-IUD, the expression of VEGF mRNA was 0.425 +/- 0.019 (P < 0.05). There were no significant changes in the level of VEGF protein and mRNA, as well as KDR in endometrium before and after insertion of FICu-IUD. Compared with before insertion of FCu-IUD 15.4 +/- 2.8, a significant increase in MVD was observed after insertion of FCu-IUD 19.8 +/- 4.8, and the expression of VEGF protein was positively correlated with MVD (r = 0.847, P < 0.01). MVD counts were not different significantly before and after insertion of FICu-IUD. CONCLUSIONS: FCu-IUD can enhance the expression of VEGF and KDR in the endometrium. FICu-IUD can inhibit the activity of VEGF and KDR by releasing indomethacin. VEGF and KDR may be related to the structural and functional changes of microvessels in endometrium after insertion of FCu-IUD or FICu-IUD.