Improvement of mechanical heart function by trimetazidine in db/db mice  

作　　者：Yuan-jing LI Pei-hua WANG Chen CHEN Ming-hui ZOU Dao-wen WANG 

机构地区：[1]Department of Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China [2]Department of Medicine and Endocrinology, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

出　　处：《Acta Pharmacologica Sinica》2010年第5期560-569,共10页中国药理学报（英文版）

基　　金：Acknowledgements This work was supported by the National Basic Research Program of China （973 Program） （No 2007CB512004）, National Natural Science Foundation of China （No 30770882） and Wuhan City grants.

摘　　要：Aim： To investigate the influence of trimetazidine, which is known to be an antioxidant and modulator of metabolism, on cardiac function and the development of diabetic cardiomyopathy in db/db mouse. Methods： Trimetazidine was administered to db/db mice for eight weeks. Cardiac function was measured by inserting a Millar catheter into the left ventricle, and oxidative stress and AMP-activated protein kinase （AMPK） activity in the myocardium were evaluated. Results： Untreated db/db mice exhibited a significant decrease in cardiac function compared to normal C57 mice. Oxidative stress and lipid deposition were markedly increased in the myocardium, concomitant with inactivation of AMPK and increased expression of peroxisome proliferator-activated receptor coactivator-la （PGC-la）. Trimetazidine significantly improved systolic and diastolic function in hearts of db/db mice and led to reduced production of reactive oxygen species and deposition of fatty acid in cardiomyocytes. Trimetazidine also caused AMPK activation and reduced PGC-la expression in the hearts of db/db mice. Conclusion： The data suggest that trimetazidine significantly improves cardiac function in db/db mice by attenuating lipotoxicity and improving the oxidation status of the heart. Activation of AMPK and decreased expression of PGC-1α were involved in this process. Furthermore, our study suggests that trimetazidine suppresses the development of diabetic cardiomyopathy, which warrants further clinical investigation.Aim： To investigate the influence of trimetazidine, which is known to be an antioxidant and modulator of metabolism, on cardiac function and the development of diabetic cardiomyopathy in db/db mouse. Methods： Trimetazidine was administered to db/db mice for eight weeks. Cardiac function was measured by inserting a Millar catheter into the left ventricle, and oxidative stress and AMP-activated protein kinase （AMPK） activity in the myocardium were evaluated. Results： Untreated db/db mice exhibited a significant decrease in cardiac function compared to normal C57 mice. Oxidative stress and lipid deposition were markedly increased in the myocardium, concomitant with inactivation of AMPK and increased expression of peroxisome proliferator-activated receptor coactivator-la （PGC-la）. Trimetazidine significantly improved systolic and diastolic function in hearts of db/db mice and led to reduced production of reactive oxygen species and deposition of fatty acid in cardiomyocytes. Trimetazidine also caused AMPK activation and reduced PGC-la expression in the hearts of db/db mice. Conclusion： The data suggest that trimetazidine significantly improves cardiac function in db/db mice by attenuating lipotoxicity and improving the oxidation status of the heart. Activation of AMPK and decreased expression of PGC-1α were involved in this process. Furthermore, our study suggests that trimetazidine suppresses the development of diabetic cardiomyopathy, which warrants further clinical investigation.

关 键 词：cardiac protection CARDIOMYOPATHY DIABETES diabetic cardiovascular complications mice MITOCHONDRIA HEART oxidative stress 

分 类 号：R[医药卫生]