| Autor: |
Cai H; Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China., Zhang G; Department of Geriatrics and Gerontology, Beijing Huaxin Hospital, the First Affiliated Hospital of Tsinghua University, Beijing, China., Chen W; Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China., Zhang B; Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China., Zhang J; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing, China., Chang J; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing, China., Tang C; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing, China., Qi Y; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing, China., Yin X; Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China. |
| Abstrakt: |
Clinical studies have suggested that metformin, a widely used antidiabetic agent, exerts a direct cardioprotective effect on cardiovascular disease in addition to its blood glucose-lowering activity. This study was designed to identify the role of metformin in rats with isoproterenol (ISO)-induced myocardial injury and to investigate its underlying mechanism. A rat model of myocardial ischemic injury was established by the subcutaneous injection of a high dose of ISO, a beta-adrenergic agonist. The results showed that pretreatment of metformin significantly reduced rat mortality induced by ISO, attenuated the increased plasma lactate dehydrogenase activity and myocardium malondialdehyde level, alleviated the hemodynamic disturbance, inhibited the upregulated gene expression of myocardial probrain natriuretic peptide and alleviated the myocardial morphological injury and apoptosis induced by ISO. Furthermore, western blot analysis showed that metformin suppressed the overexpression of the endoplasmic reticulum stress (ERS) markers cleaved caspase-12 and CEBP-homologous protein induced by ISO and increased the phosphorylation of AMP-activated protein kinase (AMPK). In conclusion, these data suggest that metformin might protect the myocardium against acute ischemic injury in rats at least partially by activating AMPK and alleviating aberrant ERS. These findings might provide further experimental evidence for treating patients at risk of ischemic heart disease with metformin. |
