国际生殖健康/计划生育 ›› 2017, Vol. 36 ›› Issue (5): 373-377.

• 论著 • 上一篇    下一篇

17β-雌二醇下调MCP-1及RhoA表达发挥心血管保护作用

刘文华,张治芬,汤珊珊,陈临节,黄哲人,魏双双   

  1. 310008 杭州市妇产科医院妇产科
  • 收稿日期:2017-06-27 修回日期:2017-08-01 出版日期:2017-09-15 发布日期:2017-10-13
  • 通讯作者: 张治芬,E-mail:zhangzf@zju.edu.cn E-mail:zhangzf@zju.edu.cn
  • 基金资助:
    国家卫生和计划生育委员会科研基金(WKJ-2013-2-024);杭州市医药卫生科技计划重点项目(2011Z003);杭州市科技发展计划项目(20120533Q04)

Cardiovascular Protection of 17β-estradiol by Down-regulating the Expression of MCP-1 and RhoA

LIU Wen-hua, ZHANG Zhi-fen, TANG Shan-shan, CHEN Lin-jie,HUANG Zhe-ren, WEI Shuang-shuang   

  1. Department of Obstetrics and Gynecology, Hangzhou Maternity Hospital, Hangzhou 310008,China
  • Received:2017-06-27 Revised:2017-08-01 Published:2017-09-15 Online:2017-10-13
  • Contact: ZHANG Zhi-fen, E-mail: zhangzf@zju.edu.cn E-mail:zhangzf@zju.edu.cn

摘要: 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。

关键词: 雌二醇;沉默调节蛋白1, 腺苷酸活化蛋白激酶, 单核细胞趋化因子1, Ras同源基因家族成员A, 动物实验

Abstract: 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.

Key words:  Estradiol, Silence regulating protein 1, AMP-activated protein kinase, Monocyte chemotactic factor 1, Ras homolog gene family, member A, Animal experimentation