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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 investigate the effect of poly (ADP-ribose) synthase (PARP) inhibitor on the expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 MMP-9 and TIMP-1 gene transcription. Methods: Primary cultured and passaged neonatal SD rat cardiac fibroblasts. The cells were pretreated with PARP inhibitor 3-aminobenzamide (3-AB) to observe the effect of 3-AB on the expression of MMP-2, MMP-9 and TIMP-1 in cardiac fibroblasts induced by AngⅡ. Results: The mRNA expression of MMP-2, MMP-9 and TIMP-1 in Ang Ⅱ-stimulated cardiac fibroblasts was significantly increased, and the activity of PARP and the expression of PARP1 in fibroblasts were significantly increased. Using 3-AB to inhibit the activity and expression of PARP1, the expression of MMP-2, MMP-9 and TIMP-1 in cardiac fibroblasts induced by AngⅡwere significantly reduced. Conclusion: PARP plays an important regulatory role in Ang Ⅱ-induced cardiac remodeling.