iNOS及ERK1/2信号转导通路在17β-雌二醇抑制血管平滑肌细胞增殖中的作用  

Effect of iNOS and ERK1/2 on 17β-estradiol-induced inhibition of vascular smooth muscle cell proliferation

作　　者：刘海梅[1] 赵晓峰[2] 林桂平[3] 徐进文[3] 王庭槐[3] 

机构地区：[1]广州中医药大学生理学教研室,广东广州510006 [2]韶关学院医学院生理学教研室,广东韶关512026 [3]中山大学中山医学院生理学教研室,广东广州510080

出　　处：《心脏杂志》2009年第6期761-764,773,共5页Chinese Heart Journal

基　　金：国家自然科学基金项目资助(30440028)

摘　　要：目的:观察诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)及细胞外信号调节激酶1/2(ERK1/2)信号转导通路在17β-雌二醇(17β-estradiol,E2)抑制血管平滑肌细胞(vascular smooth muscle cells,VSMCs)增殖中的作用。方法:采用MTT比色法和Western blot技术,检测E2预处理前后胎牛血清(fetal calf serum,FCS)对VSMCs中DNA合成、iNOS表达及磷酸化的ERK1/2蛋白表达的影响。结果:E2作用24 h,可明显抑制FCS诱导的VSMCs增殖。Western blot的结果显示,FCS孵育VSMCs后,iNOS蛋白的表达下降,磷酸化的ERK1/2蛋白表达增加。E2预处理后,可增加iNOS蛋白的表达,抑制磷酸化ERK1/2蛋白表达。若提前应用iNOS阻断剂L-精氨酸甲酯(L-NAME)孵育VSMCs,可部分逆转E2诱导的磷酸化的ERK1/2蛋白表达下降的效应。结论:E2可抑制FCS诱导的VSMCs增殖,其作用可能与增加iNOS蛋白的表达,抑制磷酸化的ERK1/2表达有关。AIM： To investigate the effect of iNOS and phosphorylation of ERK1/2 on 17β-estradiol （E2）-induced inhibition of vascular smooth muscle cells （VSMCs）. METHODS： In cultured VSMCs, proliferation was determined by MTT assay, and the expression of iNOS and ERK1/2 phosphorylation were measured by Western blot. RESULTS： The measurement showed that exposure to fetal calf serum （FCS） for 24 h increased the proliferation of VSMCs. Pretreatment with E2 for 24 h inhibited VSMC proliferation under growth-stimulating （10% FCS） condition. Western blot showed that FCS inhibited expression of iNOS and increased expression of ERK1/2 phosphorylation in VSMCs. Pretreatment with E2 for 24 h partly reversed this effect. Western blot results further proved that pretreatment with iNOS inhibitor, L-NAME, partly reversed the increase of ERK1/2 phosphorylation induced by FCS. CONCLUSION： Our results demonstrate that 17β-estradiol increases iNOS expression and decreases ERK1/2 phosphorylation, leading to inhibition of VSMC proliferation.

关 键 词：17Β-雌二醇 诱导型一氧化氮合酶 细胞外信号调节激酶1/2 血管平滑肌细胞 

分 类 号：Q579.13[生物学—生物化学]