CPU0213对内皮素-NADPH氧化酶介导H_2O_2损伤心肌细胞的改善作用  

Endothelin-NADPH oxidase mediates cardiomyocytes dysfunction caused by H_2O_2 and interventions by CPU0213

作　　者：张国林[1] 徐明[1] 戴德哉[1] 奚涛[2] 戴茵[1] 

机构地区：[1]中国药科大学药理学研究室,南京210009 [2]中国药科大学生命科学与技术学院,南京210009

出　　处：《中国药科大学学报》2011年第5期452-457,共6页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.B1070145)~~

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。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 pPKCe/PKCe, NADPH oxidase and ETAR/ETBR were up-regulated in H2O2 treated group, which implyed the involvement of PKCe. Endothelin receptor antagonist CPU0213 attenuated the abnormal expression of FKBP12.6, SERCA2a and CASQ2 by inhibiting pPKC-NADPH pathway.

关 键 词：NADPH氧化酶 内皮素 FKBP12.6 SERCA2A 内皮素受体拮抗剂 CPU0213 

分 类 号：R965[医药卫生—药理学]