血管紧张素1-7对大鼠血脂及胆固醇逆转运相关因子表达的影响

Effects of Angiotensin(1-7)on the Expression of Lipids and Reverse Cholesterol Transport Related Factors in Rats

目的探讨血管紧张素1-7[Ang(1-7)]对大鼠血脂及胆固醇逆转运相关因子ATP结合盒转运子A1(ABCA1)、过氧化体增殖物激活型受体γ(PPARγ)、肝X受体α(LXRα)和视黄酸X受体α(RXRα)表达的影响。方法将40只健康雄性SD大鼠随机分为正常对照组、高脂饲料组、Ang(1-7)组及Ang(1-7)+A779组。通过植入式胶囊渗透压泵,经颈静脉插管持续给予Ang(1-7),28天后,检测各组大鼠血浆总胆固醇、甘油三酯、低密度脂蛋白胆固醇及高密度脂蛋白胆固醇水平,定量实时聚合酶链反应及Western blot检测各组大鼠动脉组织中ABCA1、PPARγ、LXRα、RXRα基因表达的变化。结果与正常对照组比较,高脂饲料组大鼠总胆固醇、甘油三酯、低密度脂蛋白胆固醇均有所升高(P<0.05),高密度脂蛋白胆固醇有所降低(P<0.05);与高脂饲料组比较,Ang(1-7)组大鼠总胆固醇、甘油三酯、低密度脂蛋白胆固醇均有所降低(P<0.05),高密度脂蛋白胆固醇有所升高(P<0.05);与Ang(1-7)组比较,Ang(1-7)+A779组大鼠总胆固醇、甘油三酯、低密度脂蛋白胆固醇均有所升高(P<0.05),高密度脂蛋白胆固醇有所降低(P<0.05)。与正常对照组比较,高脂饲料组大鼠ABCA1、PPARγ、LXRα、RXRα的mRNA和蛋白含量均有所降低(P<0.05);与高脂饲料组比较,Ang(1-7)组大鼠ABCA1、PPARγ、LXRα、RXRα的mRNA和蛋白含量均有所升高(P<0.05);与Ang(1-7)组比较,Ang(1-7)+A779组大鼠ABCA1、PPARγ、LXRα、RXRα的mRNA和蛋白含量均有所降低(P<0.05)。结论 Ang(1-7)能够降低大鼠血浆中血脂水平,促进大鼠动脉组织中ABCA1、PPARγ、LXRα、RXRα的基因表达,对高脂血症有一定的治疗作用。

Aim To investigate the effects of angiotensin （1-7） [ Ang（1-7） ] on the expression of lipids and re- verse cholesterol transport related factors ： ATP binding cassette transporter A1 （ ABCA1 ）, peroxisome proliferator-activated receptor -,/ （ PPARγ）, liver X receptor a （LXRα） and retinoid X receptor α （RXRα） in rats. Methods 40 healthy SD male rats were randomly divided into normal control group, high-fat diet group, Ang（ 1-7 ） group and Ang（ 1-7 ） ＋ A779 group. Ang （ 1-7 ） was continuably given by osmotic pump and jugular vein cannulation, after 28 d, total cholesterol （TC）, triglyceride （TG）, low density lipoprotein cholesterol （LDLC） and high density lipoprotein cholesterol （HDLC） in rat plasma were detected, gene expression of ABCA1, PPAR~, LXRc~ and RXRa in the aortic tissues of rats were meas- ured by quantitative real-time polymerase chain reaction （qRT-PCR） and Western blot. Results Compared with the normal control group, TC, TG, LDLC of high-fat diet group were increased （ P 〈 0. 05）, HDLC of high-fat diet group were lower （P 〈 0. 05） ; compared with high-fat diet group, TC, TG, LDLC of Ang（1-7） group were lower （P 〈 0. 05 ）, HDLC of Ang（ 1-7 ） group were increased （ P 〈 0. 05 ） ; compared with Ang（ 1-7 ） group, TC, TG, LDLC of Ang（ 1-7 ） ＋ A779 group were increased （ P 〈 O. 05 ）, HDLC of Ang（ 1-7 ） ＋ A779 group were lower （ P 〈 O. 05 ）. Compared with the normal control group, ABCA1, PPAR＇y, LXRot, RXRct mRNA and protein levels of high-fat diet group were lower （ P 〈 O. 05 ） ; compared with high-fat diet group, ABCA1, PPAR~, LXRct, RXRct mRNA and protein levels of Ang（ 1-7 ） group were in- creased （P 〈 0.05 ） ; compared with Ang（ 1-7 ） group, ABCA1, PPARα, LXRct, RXRct mRNA and protein levels of Ang （1-7） ＋ A779 group were lower （P 〈 0. 05 ）. Conclusion Ang （ 1-7 ） reduced the lipid levels in rat plasma, raised the gene expression of ABCA1, PPARα, LXRot and RXRct in the aortic tissues of rats, cured the hyperlipidemia.