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目的:探讨1型多聚二磷酸腺苷核糖合成酶[poly(ADP-ribose)polymerase-1,PARP-1]对去甲肾上腺素(norepinephrine,NE)诱导培养的大鼠心肌细胞重构过程中的调节作用及其机制。方法:①培养乳鼠心肌细胞,10μmol/LNE刺激心肌细胞24h后,使用实时定量PCR法检测c-fos、ANP、β-MHC、α-MHC基因表达水平;观察抗氧化剂维生素C(VitC)和PARP-1抑制剂3-氨基苯甲酰胺(3-aminobenzamide,3-AB)对上述基因表达的影响。②检测心肌细胞内活性氧(ROS)水平,及PARP活性和PARP-1表达水平的变化。结果:NE诱导心肌细胞内c-fos、ANP、β-MHC基因表达水平明显增加。心肌细胞内ROS产生增加,PARP激活,PARP-1蛋白表达亦显著增加。使用VitC减少ROS产生,抑制了NE诱导的PARP-1活性及表达的增加,NE诱导的c-fos、ANP基因表达也显著降低。3AB可明显减少NE诱导的c-fos、ANP、β-MHC基因的表达及β-MHC/α-MHC的比值。结论:NE刺激心肌细胞增加了细胞内ROS的产生,大量的ROS激活了PARP并使PARP-1的表达水平显著增加,PARP-1参与调节了心肌重构过程胚胎基因c-fos、ANP、β-MHC、α-MHC的异常表达。PARP-1可能是心肌重构过程中的重要调节机制之一。
Objective: To investigate the effect of poly (ADP-ribose) polymerase-1 (PARP-1) on the cardiomyocyte remodeling induced by norepinephrine (NE) Regulation and its mechanism. Methods: ①The cultured neonatal rat cardiomyocytes were cultured in the presence of 10μmol / LNE for 24 hours. The expression of c-fos, ANP, β-MHC and α-MHC were detected by real- Effect of PARP-1 inhibitor 3-aminobenzamide (3-AB) on the above gene expression. ② The levels of reactive oxygen species (ROS) and PARP activity and PARP-1 expression in cardiomyocytes were measured. Results: The expression of c-fos, ANP and β-MHC genes in NE-induced cardiac myocytes increased significantly. ROS production in cardiomyocytes increased, PARP activation, PARP-1 protein expression also increased significantly. VitC reduced the production of ROS, inhibited the NE-induced increase of PARP-1 activity and expression, and NE-induced c-fos and ANP gene expression were also significantly reduced. 3AB can significantly reduce the NE induced c-fos, ANP, β-MHC gene expression and β-MHC / α-MHC ratio. CONCLUSION: NE stimulates cardiomyocytes to increase intracellular ROS production. A large amount of ROS activates PARP and significantly increases the expression of PARP-1. PARP-1 is involved in the regulation of c-fos, ANP and β -MHC, α-MHC abnormal expression. PARP-1 may be one of the important regulatory mechanisms in myocardial remodeling.