性别及雌激素水平对肾血管性高血压大鼠血管组织ACE_1-AngⅡ-ATR轴的影响

Effects of sex and estrogen levels on ACE_1-Ang Ⅱ-ATR axis in renovascular hypertension rats

目的探讨性别及雌激素水平对肾血管性高血压(RVH)大鼠血管组织中血管紧张素转换酶1(ACE1)-血管紧张素Ⅱ(AngⅡ)-血管紧张素受体(ATR)轴的影响。方法45只SPF级SD大鼠制备两肾一夹(2K1C) RVH动物模型,分为雌性手术组(2K1C-F)、雄性手术组(2K1C-M)、雌性去势组(2K1C-OVX)。常规喂养32周,测量血压;取血,检测血清中雌二醇的浓度,血浆中AngⅡ的浓度;检测血管组织中ACE1、血管紧张素1型受体(AT_1R)和2型受体(AT_2R)的mRNA及蛋白表达。结果 2K1C-F组的收缩压明显高于2K1C-M组和2K1C-OVX组(P <0. 05)。2K1C-F组的AngⅡ的含量明显低于2K1C-M组和2K1C-OVX组(P<0. 01)。与2K1C-F组相比,2K1C-M组ACE1、AT_1R、AT_2R的mRNA及蛋白表达明显上调(P <0. 05),2K1C-OVX组ACE1、AT_1bR的mRNA表达明显上调(P <0. 05),AT_2R的mRNA表达明显下调(P <0. 05);与2K1C-M组比较,2K1COVX组ACE1、AT_1bR、AT_2R mRNA的表达,以及ACE1、AT_2R的蛋白表达明显下调(P <0. 05)。结论血管组织中ACE1、AngⅡ、AT_1aR、AT_1bR的mRNA及蛋白表达存在性别及雌激素差异性,雌激素可降低ACE1-AngⅡ-AT_1R轴的活性。

Aim To investigate the effects of gender differences and estrogen levels on ACE 1-Ang Ⅱ-ATR axis in the aorta tissue of renovascular hypertension(RVH) rats. Methods Forty-five rats were made two-kidney one-clip(2K1C) model of renovascular hypertension and divided into three groups: female two kidney one clip group(2K1C-F), male two kidney one clip group(2K1C-M), and ovariectomized group(2K1C-OVX). After 32 weeks of routine feeding, the blood pressure was measured, blood was taken andserum and plasma were prepared. Serum estrogen and plasma Ang Ⅱ were measured and mRNA and protein expression levels of ACE 1, AT 1R, AT 2R in aorta tissue were detected. Results Systolic blood pressure of 2K1C- F group was significantly higher than that of 2K1C-M group and 2K1C-OVX group( P <0.05). The content of Ang Ⅱ in 2K1C-F group was significantly lower than that in 2K1C-M and 2K1C-OVX group( P <0.01). Compared with 2K1C-F group, the mRNA and protein expressions of ACE 1,AT 1R ,AT 2R in 2K1C-M group were up-regulated significantly( P <0.05), while the mRNA expression of AT 1b R, ACE 1 was up-regulated, and the mRNA expression of AT 2R was down-regulated in 2K1C-OVX group( P <0.05);compared with 2K1C-M group, the mRNA expression of ACE 1,AT 1b R ,AT 2R and protein expression of ACE 1, AT 2R were down-regulated significantly in 2K1C-OVX group( P <0.05). Conclusions The mRNA and protein expressions of ACE 1, Ang Ⅱ, AT 1a R and AT 1b R in aorta tissue show gender and estrogen differences, and estrogen can reduce the activity of ACE 1-Ang Ⅱ-AT 1R axis.