非诺贝特和吡格列酮对血管紧张素Ⅱ介导的心肌细胞肥大和凋亡的干预作用

Fenofibrate and Pioglitazone Reduce Angiotensin Ⅱ Induced Hypertrophy and Apoptosis in Cardiomyocytes in Rat

目的探讨过氧化物酶体增殖物激活型受体α和γ(PPARα和PPARγ)的配体非诺贝特、吡格列酮对血管紧张素Ⅱ(AngⅡ)诱导的心肌细胞肥大、凋亡的干预作用,并观察其对凋亡相关基因Bcl-2/Bax表达变化的影响。方法分别以非诺贝特和/或吡格列酮预处理体外原代培养的新生大鼠心肌细胞24h后,再加用AngⅡ作用24h。采用软件分析细胞表面积,用流式细胞仪检测细胞凋亡率,用Western-blot法观察凋亡相关基因Bcl-2/Bax的表达变化,逆转录聚合酶链反应检测PPARα和PPARγ的mRNA水平。结果与AngⅡ组比较,非诺贝特组、吡格列酮组及非诺贝特和吡格列酮组的心肌细胞表面积、细胞凋亡率及Bax蛋白的表达明显降低(P<0.05),而Bax蛋白的表达和Bcl-2/Bax蛋白水平比值显著增加(P<0.05),非诺贝特组、吡格列酮组及非诺贝特和吡格列酮组间的上述指标差异无显著性(P>0.05),非诺贝特组的PPARαmRNA和吡格列酮组的PPARγmRNA表达增高。结论PPARα和γ激活可逆转心肌细胞肥大,抑制心肌细胞凋亡,并能改变凋亡相关基因Bcl-2/Bax的表达,但PPARα、γ配体合用无叠加效应。

objective The study was to investigate the effects of ligands of peroxisome proliferator-activated receptors （PPAR）, fenofibrate and pioglitazone, on hypertrophy and apoptosis and changes in Bcl-2 and Bax expression induced by angiotensin Ⅱ （Ang Ⅱ ） in neonatal rat cardiac myocytes. Methods Hypertrophy and apoptosis of neonatal rat cardiac myocytes was established using Ang Ⅱstimulation. The surface area of cardiac myocytes was analysis by Leca Qwin Image software. Annexin V-FITC and PI staining and then flow-cytometry were used for monitoring the apoptosis cells. The proto-oncogene Bcl-2 and Bax expression was observed by Western blot. The mRNA expression of PPARα and PPARy was assessed by reverse transcription-polymerase chain reaction. Results Fenofibrate and pioglitazone inhibited the increases in surface area in cardiae myocytes and ratio of apoptosis induced by Ang Ⅱ（P〈0. 05）. Pre-treatment with fenofibrate and pioglitazone upregulated protein expression of Bcl-2, whereas decreased Bax expression （P〈0.05）. Fenofibrate and （P〈0.05）. Conclusion These data suggest that pre-treatment with the PPARα and PPARy agonist attenuate myocardiocyte hypertrophy and apoptosis along with upregulate Bcl-2 expression and downregulate Bcl-2 expression. No synergic effect of fenofibrate and pioglitazone were found.