奥美昔芬对子宫内膜异位症模型大鼠内膜血管生成及ERK-VEGF/MMP-9通路的影响

目的 观察奥美昔芬对子宫内膜异位症模型大鼠内膜血管生成及ERK-VEGF/MMP-9通路的影响。方法 构建子宫内膜异位症模型(EM)大鼠,将其随机分为模型组、奥美昔芬组,通过皮下注射等量的0.9%生理盐水、奥美昔芬100 mg/(kg·d),连续注射42 d,测量术后14 d和48 d各组大鼠异位病灶体积,光镜下观察各组大鼠异位内膜组织形态变化,Western blot法检测大鼠子宫内膜促血管生成素1(Ang-1)、促血管生成素2(Ang-2)、细胞外信号调节激酶(ERK)、血管内皮生长因子(VEGF)、基质金属蛋白酶2(MMP-2)和基质金属蛋白酶9(MMP-9)蛋白水平情况。结果 术后14 d,与空白组相比,模型组、奥美昔芬组大鼠体内异位病灶体积显著升高(P＜0.05),在术后48 d,与空白组相比,模型组、奥美昔芬组异位病灶体积显著升高(P＜0.05),异位膜上皮细胞、血管增多,与模型组相比,奥美昔芬组异位病灶体积显著降低(P＜0.05),异位膜上皮细胞萎缩、血管减少,大鼠体内Ang-1、Ang-2、ERK、VEGF、MMP-2、MMP-9蛋白水平显著降低(P＜0.05)。结论 奥美昔芬可能通过调控ERK-VEGF/MMP-9,降低Ang-1、Ang-2蛋白表达,抑制内膜血管生成。

Effects of olmecxifene on angiogenesis and ERK-VEGF/MMP-9 pathway in endometriosis model rats

Objective To observe the effects of olmecxifen on angiogenesis and ERK-VEGF/MMP-9 pathway in endometriosis model rats.Methods The endometriosis model (EM)rats were established and randomly divided into model group,omeprazole group,the same amount of 0.9% normal saline,olmecxifene 100 mg/(kg·d)were given by subcutaneous injection continuously for 42 d,the volume of heterotopic focus was measured at 14 d and 48 d after operation,the morphological changes of ectopic endometrium were observed under light microscope,and the levels of angiopoietin-1(Ang-1),angiopoietin-2 (Ang-2),extracellular signal regulated kinase(ERK),vascular endothelial growth factor(VEGF),matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9(MMP-9)proteins in endometrium were measured by Western blot.Results On the 14th day after operation,compared with the blank group,the volume of ectopic focus in the model group and olmecxifene group increased significantly(P＜0.05),on the 48th day after operation,compared with the blank group,the volume of ectopic focus in the model group and the omeprazole group increased significantly(P＜0.05),and ectopic membrane epithelial cells and blood vessels increased,compared with the model group,the volume of ectopic focus was significantly reduced(P＜0.05),the ectopic membrane epithelial cells atrophied and the blood vessels decreased,and the protein levels of Ang-1,Ang-2,ERK,VEGF,MMP-2 and MMP-9 in rats were significantly decreased(P＜0.05).Conclusions Olmecxifene may reduce the expressions of Ang-1 and Ang-2 proteins and inhibit the angiogenesis of endometrium by regulating ERK-VEGF/MMP-9.