Early administration of trimetazidine attenuates diabetic cardiomyopathy in rats by alleviating fibrosis, reducing apoptosis and enhancing autophagy

细胞凋亡 内科学 氧化应激 心功能曲线 PI3K/AKT/mTOR通路 标记法 内分泌学 蛋白激酶B 心脏纤维化 心肌病
作者
Lei Zhang,Wen-Yuan Ding,Zhi-Hao Wang,Meng-xiong Tang,Feng Wang,Ya Li,Ming Zhong,Yun Zhang,Wei Zhang
出处
期刊:Journal of Translational Medicine [Springer Nature]
卷期号:14 (1): 109-109 被引量:47
标识
DOI:10.1186/s12967-016-0849-1
摘要

Trimetazidine, as an anti-ischemic and antioxidant agent, has been demonstrated to have many cardioprotective effects. However, whether early administration of trimetazidine has an effect on diabetic cardiomyopathy and the mechanisms underlying the effect have not yet been elucidated. We established a type 2 DCM rat model by high-fat diet and low-dose streptozotocin. Rats were separated into different groups: control, diabetes, and diabetes + trimetazidine (n = 6, each). Cardiac autophagy, cardiac functions, and cardiomyocyte apoptosis were monitored. Rats with type 2 DCM showed severe insulin resistance, left ventricular dysfunction, increased cardiomyocyte apoptosis, and reduced cardiac autophagy. Collagen volume fraction (CVF) and perivascular collagen area/luminal area (PVCA/LA) ratio were significantly higher in the diabetic group than the control group. We found that trimetazidine treatment ameliorated metabolic disturbance and insulin resistance, reduced cardiomyocyte apoptosis, and restored cardiac autophagy. CVF and PVCA/LA ratio were also lower in the diabetes + trimetazidine group than the diabetic group (CVF, 4.75 ± 0.52 % vs. 11.04 ± 1.67 %, p < 0.05; PVCA/LA, 8.37 ± 0.51 vs. 17.97 ± 2.66, p < 0.05). Furthermore, trimetazidine inhibited phosphorylation of ERK and P38 MAPK to reduce myocardial fibrosis. Inhibited phosphorylation of AMPK was restored and the interaction between Bcl-2 and Beclin1 was enhanced in diabetes + trimetazidine group, resulting in the initiation of autophagy and alleviation of apoptosis. Early administration of trimetazidine could ameliorate diabetic cardiomyopathy by inhibiting myocardial fibrosis and cardiomyocyte apoptosis and enhancing autophagy. Therefore, trimetazidine may be a good choice in the prevention of diabetic cardiomyopathy if applied at the early stage of diabetes.
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