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目的:观察多聚二磷酸腺苷(ADP)核糖合成酶(PARP)抑制剂对血管紧张素Ⅱ(AngⅡ)刺激的乳鼠心脏心肌重构的预防作用。方法:新生大鼠心肌细胞原代培养,传代,用PARP抑制剂3-AB预处理细胞,观察PARP抑制剂对AngⅡ诱导心肌细胞PARP激活、PARP1表达,细胞内ROS产生和c-fos,ANP,β/αMHC基因表达的影响。结果:AngⅡ显著诱导心肌细胞PARP激活,ROS产生增加,PARP1、c-fos、β/α-MHC、ANP基因表达增加。给予3-AB预处理可显著抑制AngⅡ诱导的上述变化。结论:AngⅡ可以诱导培养的心肌细胞内PARP激活,PARP1蛋白表达增加,3-AB预处理可以明显降低AngⅡ诱导的心肌细胞内异常基因表达增加,提示PARP1参与了心室重构的发生发展过程。
Objective: To observe the preventive effect of poly (ADP - ribose) synthase (PARP) inhibitor on cardiomyocyte remodeling induced by angiotensin Ⅱ (Ang Ⅱ) in neonatal rat hearts. Methods: Primary cultured neonatal rat cardiomyocytes were passaged and pretreated with PARP inhibitor 3-AB. The effects of PARP inhibitor on PARP activation, PARP1 expression, intracellular ROS production and c-fos, ANP, β / αMHC gene expression. RESULTS: Ang Ⅱ significantly induced PARP activation, increased ROS production and increased expression of PARP1, c-fos, β / α-MHC and ANP. Administration of 3-AB pretreatment significantly inhibited AngⅡ-induced changes. CONCLUSION: AngⅡ can induce the activation of PARP in cultured cardiomyocytes and increase the expression of PARP1 protein. 3-AB preconditioning can significantly reduce the abnormal gene expression induced by AngⅡ in cardiomyocytes, suggesting that PARP1 is involved in the development of ventricular remodeling.