17β-雌二醇下调MCP-1及RhoA表达发挥心血管保护作用

摘要

Objective:To observe the regulation of estrogen on the expressions of Monocyte chemotactic factor 1 (MCP-1) and Ras homolog gene family member A (RhoA) in female ovariectomized Sprague-Dawley rats,so as to study the protective effect of estrogen on cardiovascular system.Methods:Forty five female rats aged 12 weeks were randomly divided into five groups:the blank control group (CON,n=10),the ovariectomized group (OVX,n=12),the estrogen-treated group with 17β-estradiol (OVX+E2,n=13) and the sham-operated group (SHAM,n=10).200 μg/(kg·d) 17β-estradiol was administered in the OVX+ E2 group for 16 weeks,the other three groups were given equal normal saline.After 16 weeks,the levels of serum estradiol (E2),follicle-stimulating hormone (FSH),monocyte chemotactic factor 1 (MCP-1) and RhoA were measured by ELISA;the heart tissue was harvested and weighted,the morphological change was observed by HE staining.The levels of tissue silence regulating protein 1 (SIRT1),activated protein kinase (AMPK) were measured by ELISA.The expressions of MCP-1 and RhoA were detected by immunofluorescence histochemistry.Results:The levels of serum and heart tissue RhoA and MCP-1 in the OVX+E2 group were significantly lower than those in the OVX group (P＜0.05).The levels of heart tissue SIRT1 and AMPK in the OVX+E2 group were significantly higher than those in the OVX group (P＜0.05).Conclusions:The estrogen replacement plays a protective effect in those female ovariectomized rats by down-regulating the expressions of serum and heart tissue MCP-1 and RhoA.The potential mechanism is that the AMPK/SIRT1 pathway may be up-regulated by 17β-estradiol.%目的:探讨雌激素对去势雌性Sprague-Dawley大鼠单核细胞趋化因子1(MCP-1)及Ras同源基因家族成员A (RhoA)水平的调控及其机制,研究雌激素对心血管的保护作用.方法:将45只3月龄雌性Sprague-Dawley大鼠随机分为空白对照组(CON,n=10)、假手术组(SHAM,n=10)、去势对照组(OVX,n=12)和去势实验组(OVX+E2,n=13).去势实验组给予200 μg/(kg·d) 17β-雌二醇灌胃,余3组给予等量生理盐水灌胃.灌胃16周后酶联免疫吸附测定(ELISA)法测定血清雌二醇(E2)、卵泡刺激素(FSH)、MCP-1及RhoA水平;ELISA法检测心脏组织沉默调节蛋白1(SIRT1)、腺苷酸活化蛋白激酶(AMPK)水平.免疫组织化学法检测心脏组织MCP-1及RhoA水平.结果:灌胃16周后去势实验组血清及心脏组织MCP-1、RhoA水平低于去势对照组(P＜0.05);去势实验组心脏组织匀浆SIRT1、AMPK水平高于去势对照组(P＜0.05).结论:外源性17β-雌二醇可下调去势雌性大鼠血清及心脏组织MCP-1,RhoA表达水平,从而发挥其心血管保护作用.其可能的机制是17β-雌二醇通过上调AMPK/SIRT1调控MCP-1及RhoA的表达水平.