Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway
Tetrahydrocurcumin Ameliorates Diabetic Cardiomyopathy by Attenuating High Glucose-Induced Oxidative Stress and Fibrosis via Activating the SIRT1 Pathway
复制标题
四氢姜黄素通过激活 SIRT1 通路减轻高血糖引起的氧化应激和纤维化，从而改善糖尿病心肌病
DOI：
10.1155/2019/6746907
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发表时间：
2019-01-01
影响因子：
--
通讯作者：
Wang, Siwang
中科院分区：
文献类型：
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作者：
Li, Kaifeng;Zhai, Mengen;Wang, Siwang
高血糖引起的氧化应激和纤维化在糖尿病心肌病（DCM）的发展中起着至关重要的作用。四氢姜黄素 (THC) 是天然抗氧化剂姜黄素的主要生物活性代谢物，据报道具有更有效的抗氧化和卓越的抗纤维化特性以及抗炎和抗糖尿病能力。本研究旨在研究 THC 对实验性 DCM 的潜在保护作用及其潜在机制，指出高葡萄糖诱导的氧化应激和相关纤维化的作用。在 STZ 诱导的糖尿病小鼠中，口服 THC（120 mg/kg/d）12 周可显着改善心脏功能，改善心肌纤维化和心脏肥大，同时减少活性氧（ROS）的产生。从机械角度来看，THC 给药显着增加了 SIRT1 信号通路在体外和体内的表达，进一步证明了下游分子 Ac-SOD2 的减少和脱乙酰化 SOD2 的产生增强，最终通过 SOD 和 GSH-Px 的修复活性增强了抗氧化应激能力，并减少了 MDA 的产生。此外，THC 治疗通过抑制 ROS 诱导的 TGFβ1/Smad3 信号通路，随后减少心脏纤维化标志物 α-SMA、胶原蛋白 I 和胶原蛋白 III 的表达来实现其抗纤维化作用。总的来说，这些发现证明了 THC 治疗主要通过激活 SIRT1 途径减轻高血糖诱导的氧化应激和纤维化来缓解 DCM 的治疗潜力。
Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM). Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities. This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis. In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation. Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production. Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III. Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.