ROS调控MMPs对子宫内膜崩解的作用

ROS Regulated MMPs to the Endometrial Breakdown

子宫内膜周期性的剥脱是高等灵长类动物特有的生理现象。活性氧(ROS)在女性生殖系统的生理过程具有重要的作用。本研究的目的是试图弄清ROS是否对子宫内膜的剥脱起作用以及通过调控金属基质蛋白酶(MMPs)起作用。本研究采用雌性C57小鼠去势,序惯性地给予雌孕激素模拟增殖期和分泌期,花生油注射至宫腔以人工诱导蜕膜化,将孕酮皮埋管移除以造成孕酮的撤退,建立小鼠月经样模型,并在孕酮撤退前1 h、3 h和7 h给予抗氧化剂NAC消除ROS;利用大体和组织形态学方法检测子宫内膜的状态,显示350 mg/kg NAC能够抑制子宫内膜的剥脱;利用Western方法检测ROS在月经发生过程中对MMP-2、MMP-9和MMP-13的调控作用,显示NAC处理组与对照组比,NAC能够抑制MMP-9在24 h的表达,也能够抑制MMP-13在16 h和24 h的表达,但并不能抑制MMP-2在16 h和24 h的表达。因此,ROS在小鼠月经样模型中通过调控MMPs特别是MMP-9和MMP-13对子宫内膜的崩解起至关重要的作用。

Endometrial breakdown is an unique physiological character to primate.Reactive oxygen species（ROS）plays an important role to female reproduction.Our aims did attempt to understand whether the ROS regulates matrix metalloproteinase（MMP） on endometrial breakdown in mouse menstrual-like model.In this study,female C57 mice were ovariectomized and treated with the hormone to mimic the proliferation and secretory period.After oil was injected into uterus luminal,49 h later,P4 explant was removed to mimic the P4 withdrawal to build the mouse menstrual-like model.The dose of NAC（350 mg/kg） was administrated to mice at-1 h（P4 withdrawal was regarded as 0 h）,3 h,7 h and 11 h to exclave the ROS.The uterus was assayed by morphological and histomorphological method,which showed that 350 mg/kg NAC inhibits the endometrial breakdown.Further,the effect of ROS on the expression of MMP-2,MMP-9 and MMP-13 by Western blot assay in the uterus were measured,which showed that NAC inhibits MMP-9 protein at 24 h,MMP-13 at 16 h and 24 h,but does not inhibit MMP-2 at 16 h and 24 h.Therefore we concluded that ROS may regulate the MMPs,especially MMP-9 and MMP-13,on the endometrial breakdown.