School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.
College of Biology, Hunan University, Changsha, 410012, China.
J Pharmacol Sci. 2019 Apr;139(4):311-318. doi: 10.1016/j.jphs.2019.01.016. Epub 2019 Mar 15.
Diabetic cardiomyopathy (DCM) is characterized by cardiac hypertrophy, fibrosis, oxidative stress and inflammation. Trimetazidine (TMZ), a potent metabolism modulator, has been shown to be cardioprotective in experimental models of ischaemia-reperfusion and type 2 diabetes-induced cardiomyopathy. The present study examined whether TMZ inhibits cardiomyopathy induced by insulin-dependent type 1 diabetes. Wistar rats were randomly divided into control group (vehicle alone), diabetes mellitus (DM; induced by streptozocin (STZ) injection) group and DM treated with TMZ (DM/TMZ) group. Cardiac function, histology, plasma biochemistry and molecular mechanism were assessed. STZ induced diabetes in rats as indicated by hyperglycemia, increased and decreased levels of advanced glycation end products (AGEs) and insulin respectively. Diabetic rats were characterized by left ventricular dysfunction, cardiachypertrophy and fibrosis and signs of inflammation and oxidative stress in the myocardium, which were accompanied by elevated levels of NADPH oxidase 2 (Nox2) and transient receptor potential channel 3 (TRPC3) in the heart. TMZ treatment ameliorated diabetes-associated structural and functional alterations by inhibiting Nox2 and TRPC3 without having any effects on glucose, insulin and AGEs levels. These results suggest that TMZ could be used as a therapy to treat cardiomyopathy associated with type 1 induced diabetes mellitus.
糖尿病心肌病（DCM）的特征是心脏肥大、纤维化、氧化应激和炎症。曲美他嗪（TMZ）作为一种有效的代谢调节剂，已被证明在缺血再灌注和 2 型糖尿病诱导的心肌病的实验模型中具有心脏保护作用。本研究探讨了 TMZ 是否抑制胰岛素依赖性 1 型糖尿病引起的心肌病。Wistar 大鼠随机分为对照组（单独给予载体）、糖尿病组（链脲佐菌素（STZ）注射诱导）和 TMZ 治疗的糖尿病组（DM/TMZ 组）。评估了心脏功能、组织学、血浆生化和分子机制。STZ 诱导大鼠糖尿病，表现为高血糖、晚期糖基化终产物（AGEs）水平升高和胰岛素水平降低。糖尿病大鼠表现为左心室功能障碍、心脏肥大和纤维化，以及心肌炎症和氧化应激的迹象，这与心脏中 NADPH 氧化酶 2（Nox2）和瞬时受体电位通道 3（TRPC3）水平升高有关。TMZ 通过抑制 Nox2 和 TRPC3 改善了与糖尿病相关的结构和功能改变，而对葡萄糖、胰岛素和 AGEs 水平没有影响。这些结果表明，TMZ 可用于治疗与 1 型糖尿病相关的心肌病。
