Resveratrol ameliorates podocyte damage in diabetic mice via SIRT1/PGC-1 mediated attenuation of mitochondrial oxidative stress
Resveratrol ameliorates podocyte damage in diabetic mice via SIRT1/PGC-1 mediated attenuation of mitochondrial oxidative stress
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白藜芦醇通过 SIRT1/PGC-1 介导的线粒体氧化应激减弱减轻糖尿病小鼠足细胞损伤
DOI：
10.1002/jcp.27306
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发表时间：
2019
影响因子：
5.6
通讯作者：
Li Ying
中科院分区：
文献类型：
--
作者：
Zhang Tao;Chi Yanqing;Kang Yingli;Lu Hua;Niu Honglin;Liu Wei;Li Ying
线粒体活性氧（ROS）的过量产生被认为是糖尿病肾病（DN）发展的起始事件。共激活子 PGC-1α 及其下游转录因子 NRF1 和 TFAM 介导的线粒体生物合成可能是维持线粒体功能的关键靶标。白藜芦醇 (RESV) 是一种天然多酚抗氧化剂，是一种有效的 SIRT1 激动剂。在本研究中，我们建立了糖尿病小鼠和暴露于高糖的足细胞作为体内和体外模型，以研究RESV对肾脏保护的功效和机制。我们发现RESV减轻了糖尿病小鼠的蛋白尿，降低了肾皮质中丙二醛含量，增加了Mn-SOD活性，抑制了肾小球足细胞和肾小管上皮细胞的凋亡，改善了病理表现，并恢复了DN小鼠肾组织中SIRT1和PGC-1α的表达。在暴露于高葡萄糖的足细胞中，RESV 抑制过量的 ROS 产生和细胞凋亡。此外，RESV还减少了线粒体ROS的产生，提高了呼吸链复合物I和III的活性，升高了线粒体膜电位，并抑制了线粒体中Cyto C和Diablo释放到细胞质中。综上所述，我们的研究结果表明 RESV 通过 SIRT1/PGC-1α 介导的线粒体氧化应激减弱来改善糖尿病小鼠的足细胞损伤。
Excessive generation of mitochondrial reactive oxygen species (ROS) is considered to be initiating event in the development of diabetic nephropathy (DN). Mitochondrial biosynthesis mediated by coactivator PGC‐1α and its downstream transcription factors NRF1 and TFAM may be a key target in maintaining mitochondrial function. Resveratrol (RESV), a natural polyphenolic antioxidant, is a potent SIRT1 agonist. In this study we established diabetes mouse and podocyte exposed to high glucose as in vivo and in vitro models to investigate the efficacy and mechanism of RESV on renoprotection. We found that RESV alleviated proteinuria of diabetic mice, decreased malondialdehyde content while increased Mn‐SOD activity in renal cortex, inhibited the apoptosis of glomerular podocytes and renal tubular epithelial cells, ameliorated pathological manifestations, and restored the expression of SIRT1 and PGC‐1α in renal tissues of DN mice. In podocytes exposed to high glucose, RESV inhibited excessive ROS production and apoptosis. In addition, RESV decreased mitochondrial ROS production, improved respiratory chain complex I and III activity, elevated mitochondrial membrane potential, and inhibited the release of Cyto C and Diablo in the mitochondria into the cytoplasm. Taken together, our findings suggest that RESV ameliorates podocyte damage in diabetic mice via SIRT1/PGC‐1α mediated attenuation of mitochondrial oxidative stress.