多聚二磷酸腺苷核糖合成酶抑制剂对血管紧张素Ⅱ诱导心脏成纤维细胞基质金属蛋白酶表达的影响

Inhibition of poly(ADP-ribose) polymerase prevented angiotensin Ⅱ induced expression of matrix metalloprotease in cardiac fibroblast

目的:观察多聚二磷酸腺苷核糖合成酶(PARP)抑制剂对血管紧张素Ⅱ(AngⅡ)刺激的乳鼠心脏成纤维细胞基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)和金属蛋白酶组织抑制剂-1(TIMP-1)基因转录的影响。方法:新生SD大鼠心脏成纤维细胞原代培养,传代。用PARP抑制剂——3-氨基苯甲酰胺(3-AB)预处理细胞,观察3-AB对AngⅡ诱导心脏成纤维细胞MMP-2、MMP-9及TIMP-1基因表达的影响。结果:AngⅡ刺激心脏成纤维细胞MMP-2、MMP-9及TIMP-1基因表达明显增加,成纤维细胞内PARP活性及PARP1的表达显著增强。使用3-AB抑制PARP1的活性及表达,可以明显降低AngⅡ诱导的心脏成纤维细胞MMP-2、MMP-9及TIMP-1基因表达的增加。结论:PARP在AngⅡ诱导的心脏重构过程中发挥了重要的调控作用。

Objective：To study the effect of poly（ADP-ribose） polymerase（PARP） inhibitor on cardiac fibroblast treated by angiotensin Ⅱ （Ang Ⅱ ）. Method： Cultured 3rd passage cardiac fibroblasts were incubated with PARP inhibitor 3-aminobenzamide （3-AB） for 30 minutes first and then 0.1μmol/L Ang Ⅱ were added to the culture medium. The incubation time was 24 hours. We explored the reactive oxygen species（ROS）, the PARP activity and the expression of MMP-2, MMP-9 and TIMP-1 in cardiac fibroblast. Result： Ang Ⅱ induced ROS generation,induced PARP activation and PARP1 expression, 3-AB effectively prevented the expression of matrix MMP- 2, MMP-9 and TIMP-1 in cultured fibroblast treated with Ang Ⅱ. Conclusion：Inhibition of PARP activation prevented Ang Ⅱ induced transcriptional expression of MMP-2, MMP-9 and TIMP-1 in cultured fibroblast.