【摘要】 心肌细胞中NADPH氧化酶活性增强和内皮素系统过度激活,是造成心肌细胞损伤的重要机制。本文旨在探讨内皮素受体拮抗剂CPU0213能否通过抑制ET-NADPH氧化酶的过表达,减轻心肌细胞氧化损伤。将SD乳大鼠心肌细胞分成7组:对照组、H2O2组、PKA/PKC阻断剂H89/Bis干预组、,NADPH氧化酶阻断剂APO/DPI组和CPU0213治疗组。结果表明,H2O2组钙调蛋白FKBP12.6,SERCA2a和CASQ2表达明显下调,pPKCε/PKCε,NADPH氧化酶亚基及ETAR/ETBR明显上调,提示:H2O2激活NADPH氧化酶须依赖PKC活性,CPU0213通过抑制ET-pPKC-NADPH氧化酶通路逆转FKBP12.6,SERCA2a和CASQ2的下调。更多还原

【Abstract】 Over-activated NADPH oxidase and endothelin(ET) system are the main mechanism of cardiomyocytes dysfunction.This research mainly focuses on the hypothesis that CPU0213 attenuates cardiomyocytes dysfunction by inhibiting the over-expression of ET-NADPH oxidase.Cardiomyocytes were divided into groups:control,H2O2 group,H89/Bis,APO/DPI,CPU0213 group.The expression of FKBP12.6,SERCA2a and CASQ2 were down-regulated and pPKCε/PKCε,NADPH oxidase and ETAR/ETBR were up-regulated in H2O2 treated group,which implyed the involvement of PKCε.Endothelin receptor antagonist CPU0213 attenuated the abnormal expression of FKBP12.6,SERCA2a and CASQ2 by inhibiting pPKC-NADPH pathway.更多还原