依普利酮对血管紧张素Ⅱ诱导心脏成纤维细胞增殖的影响

Effect of eplerenone on AngⅡ-induced proliferation of cardiac fibroblasts

目的:探讨依普利酮(eplerenone, EPL)对血管紧张素Ⅱ(angiotensinⅡ, AngⅡ)诱导心脏成纤维细胞(cardiac fibroblasts, CFs)增殖的影响。方法:利用AngⅡ刺激CFs建立心肌纤维化的细胞模型,并给予依普利酮、Nrf2抑制剂Brusatol干预,采用CCK-8法检测细胞增殖率,Western blot法检测FN和CTGF、Nrf2和HO-1蛋白表达水平。结果:1μmol·L-1 AngⅡ刺激CFs 24 h,细胞增殖率、FN和CTGF蛋白表达显著升高,Nrf2和HO-1蛋白表达显著降低(P<0.05);给予依普利酮干预后,与AngⅡ组比较,细胞增殖率、FN和CTGF蛋白表达显著降低,Nrf2和HO-1蛋白表达显著上调(P<0.05);利用Brusatol抑制Nrf2活性,与AngⅡ+EPL组比较,可逆转上述蛋白表达。结论:依普利酮能减轻AngⅡ诱导的心肌纤维化,其可能的机制与激活Nrf2/HO-1信号通路,降低FN和CTGF蛋白表达有关。

OBJECTIVE To explore the effect of eplerenone(EPL) on Ang Ⅱ-induced proliferation of cardiac fibroblasts.METHODS Cardiac fibroblasts(CFs) were treated with Ang Ⅱ, EPL and brusatol. The proliferation rate of CFs was measured by CCK-8 assay. And the protein expressions of FN and CTGF, Nrf2 and HO-1 were detected by Western blot.RESULTS After 24-hour treatment with 1 μmol·L-1 Ang Ⅱ, the proliferation rate and protein expressions of FN and CTGF significantly increased while protein expressions of Nrf2 and HO-1 significantly decreased(P<0.05). After a treatment of EPL, the proliferation rate and protein expressions of FN and CTGF significantly decreased and protein expressions of Nrf2 and HO-1 significantly increased as compared with Ang Ⅱ group;After a treatment of Brusatol, the change of protein was reversed as compared with Ang Ⅱ+EPL group.CONCLUSION Eplerenone significantly attenuates the Ang Ⅱ-induced myocardial fibrosis, which is possibly related to the activation of Nrf2/HO-1 signaling pathway, the decreased protein expression of FN and CTGF.