CPU0213对内皮素-NADPH氧化酶介导H<sub>2</sub>O<sub>2</sub>损伤心肌细胞的改善作用

CPU0213对内皮素-NADPH氧化酶介导H₂O₂损伤心肌细胞的改善作用

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ET_AR/ET_BR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。

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 ET_AR/ET_BR 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.