期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep41491
关键词
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资金
- National Science Foundation of China [81470174, 81603350, 81503280, 81303264, 81403134, 81403135, 81403182]
- Excellent Civil Service Training Fund of Forth Military Medical University [4138C4IDK6]
Hyperglycemia-induced reactive oxygen species (ROS) generation contributes to development of diabetic cardiomyopathy (DCM). This study was designed to determine the effect of an antioxidant butin (BUT) on ischemia/reperfusion-induced myocardial injury in diabetic mice. Myocardial ischemia/reperfusion (MI/R) was induced in C57/BL6J diabetes mice. Infarct size and cardiac function were detected. For in vitro study, H9c2 cells were used. To clarify the mechanisms, proteases inhibitors or siRNA were used. Proteins levels were investigated by Western blotting. In diabetes MI/R model, BUT significantly alleviated myocardial infarction and improved heart function, together with prevented diabetes-induced cardiac oxidative damage. The expression of Nrf2, AMPK, AKT and GSK-3 beta were significantly increased by BUT. Furthermore, in cultured H9c2 cardiac cells silencing Nrf2 gene with its siRNA abolished the BUT's prevention of I/R-induced myocardial injury. Inhibition of AMPK and AKT signaling by relative inhibitor or specific siRNA decreased the level of BUT-induced Nrf2 expression, and diminished the protective effects of BUT. The interplay relationship between GSK-3 beta and Nrf2 was also verified with relative overexpression and inhibitors. Our findings indicated that BUT protected against I/R-induced ROS-mediated apoptosis by upregulating the AMPK/Akt/GSK-3 beta pathway, which further activated Nrf2-regulated antioxidant enzymes in diabetic cardiomyocytes exposed to I/R.
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