多聚二磷酸腺苷核糖合成酶抑制剂对血管紧张素Ⅱ刺激培养心肌细胞异常基因表达的阻止作用

Inhibition of poly (ADP-ribose) polymerase prevented angiotensin Ⅱ induced abnormal gene expression in cultured cardiomyocyte

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 study the effect of poly （ADP-ribose） polymerase（PARP） inhibitor on cardiomyocyte treated by angiotensin Ⅱ （Ang Ⅱ ）. Method：Cultured cardiomyocytes were incubated with 15mmol/L 3-At3, or 1 × PBS for 30 minutes first and then 0. 1 μmol/L Ang Ⅱ were added to the culture medium. The incubation time for AnglI treatment was 24 hours. Then the reactive oxygen species（ROS）, PARP activity and the expression of PARP1 protein,c-fos,β/α-MHC, A-NP mRNA were measured with TCP precipitation method, fluorescent intensity detector, western blots, and real-time RT-PCR respectively. Result：Ang Ⅱ induced ROS generation, PARP activation and PARP1 expression, abnormal expression of c-fos,β/α-MHC,ANP mRNA in cultured caridomyocyets; PARP inhibitor 3-AB pretreatment significantly attenuated the effect. Conclusion：PARP inhibitor could ameliorate the effec induced by Ang Ⅱ on cardiomyocyte,protect cardiomyocyte from remodeling induced by Ang Ⅱ.