吡格列酮通过调控Sirt3改善高血压引起的心肌纤维化机制

doi:10.6040/j.issn.1671-7554.0.2016.1378

摘要/Abstract

摘要： 目的探讨吡格列酮对高血压引起的心肌纤维化的作用及可能机制。方法提取新生SD大鼠心肌成纤维细胞,分为空白对照组、单纯刺激组(血管紧张素Ⅱ 1 μmol/L)、单纯药物组(吡格列酮10 μmol/L)、刺激+药物组、沉默信息调节相关因子3(Sirt3)小干扰+刺激组和Sirt3小干扰+刺激+药物组,采用Western blotting法检测平滑肌肌动蛋白(a-SMA)、β-链蛋白(β-catenin)、胶原I(COL I)和Sirt3等蛋白含量;采用RT-PCR法检测a-SMA、Sirt3、β-catenin和COL I等mRNA表达量;采用细胞免疫荧光法检测COL I表达。结果与空白对照组相比,单纯刺激组a-SMA和COL I的mRNA和蛋白表达明显增加,Sirt3表达减少,β-catenin表达增加,COL I绿色荧光增强,心肌纤维化明显(P<0.05);与单纯刺激组相比,刺激+药物组a-SMA和COL I的mRNA和蛋白表达明显减少,Sirt3表达增加,β-catenin表达减少,COL I绿色荧光减弱,心肌纤维化明显改善(P<0.05);与药物+刺激组相比,Sirt3小干扰+药物+刺激组a-SMA、COL I的mRNA和蛋白表达增加,Sirt3表达减少,β-catenin表达增多,COL I绿色荧光增强(P<0.05)。单纯药物组与药物+刺激组相比,a-SMA、COL I、β-catenin和Sirt3的mRNA和蛋白表达无明显变化(P>0.05);Sirt3小干扰+刺激组和Sirt3小干扰+药物+刺激组相比,a-SMA、COL I、β-catenin、Sirt3的mRNA和蛋白表达无明显变化(P>0.05)。结论吡格列酮能改善高血压心肌纤维化,其作用机制可能与Sirt3激活和β-catenin抑制有关。

关键词: β-链蛋白, 吡格列酮, 高血压, 心肌纤维化, 沉默信息调节相关因子3

Abstract: Objective To investigate the effect of pioglitazone on cardiac fibrosis induced by hypertension and the possible mechanism. Methods Cardiac fibroblasts were extracted from newly-born SD rats and divided into 6 groups: negative control group, angiotension II(ANGII 1 μmol/L)group, pioglitazone(Piog 10 μmol/L)group, Piog+ANGII group, Sirt3.siRNA+ANGII group, and Sirt3.siRNA+Piog+ANGII group. The protein expressions of a-SMA, Sirt3, COL I and β-catenin were detected with Western blotting. The mRNA expressions of a-SMA, Sirt3, COL I and β-catenin were detected with quantitative real time PCR. The expression of COL I was evaluated with immuofluorescence staining. Results Compared with the negative control group, the ANGII group showed increased mRNA and protein expressions of a-SMA, COL I and β-catenin, decreased expression of Sirt3, enhanced green fluorescence of COL I, and severer cardiac fibrosis(all P<0.05). Compared with the ANGII group, the Piog+ANGII group 山东大学学报 (医学版)55卷5期 -严芳英,等.吡格列酮通过调控Sirt3改善高血压引起的心肌纤维化机制 \=-showed increased mRNA and protein expressions of Sirt3, decreased expressions of a-SMA, COL I and β-catenin, lower green fluorescence intensity of COL I, and improved cardiac fibrosis(all P<0.05). Compared with the Piog+ANGII group, the Sirt3.siRNA+Piog+ANGII group showed increased mRNA and protein levels of a-SMA, COL I and β-catenin, decreased levels of Sirt3, and higher green fluorescence intensity of COL I(all P<0.05). However, there were no significant differences in the mRNA and protein expressions between Piog and Piog+ANGII groups(P>0.05), and between Sirt3.siRNA+ANGII and Sirt3. siRNA+Piog+ANGII groups(P>0.05). Conclusion Pioglitazone can improve cardiac fibrosis induced by hypertension via activation of Sirt3 and inhibition of β-catenin.

Key words: Pioglitazone, Hypertension, Cardiac fibrosis, β-catenin, Sirtuin3

中图分类号:

R543.1

严芳英,单晓兰,李静媛,张杰,闫雪芳,杨奕,卜培莉. 吡格列酮通过调控Sirt3改善高血压引起的心肌纤维化机制[J]. 山东大学学报（医学版）, 2017, 55(5): 13-18.

YAN Fangying, SHAN Xiaolan, LI Jingyuan, ZHANG Jie, YAN Xuefang, YANG Yi, BU Peili. Pioglitazone ameliorates cardiac fibrosis induced by hypertension via regulating Sirt3[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(5): 13-18.

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