Wenxin Keli Regulates Mitochondrial Oxidative Stress and Homeostasis and Improves Atrial Remodeling in Diabetic Rats
Wenxin Keli Regulates Mitochondrial Oxidative Stress and Homeostasis and Improves Atrial Remodeling in Diabetic Rats
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DOI：
10.1155/2020/2468031
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发表时间：
2020-02-13
影响因子：
--
通讯作者：
Liu, Tong
中科院分区：
文献类型：
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作者：
Gong, Mengqi;Yuan, Ming;Liu, Tong
线粒体功能障碍和氧化应激在心房颤动（AF）和糖尿病（DM）的发病机制中起重要作用。稳心颗粒是一种抗心律失常的中药，其作用机制与调节心肌离子通道有关。本研究验证了WXKL通过恢复线粒体功能改善糖尿病大鼠心房重构的假设。将新生SD大鼠原代心房成纤维细胞分为4组：对照组、过氧化氢（H2 O2）组、H2 O2 +WXKL 1 g/L组、H2 O2 +WXKL 3 g/L组。测定细胞内线粒体膜电位（MMP）、活性氧（ROS）和线粒体耗氧量。SD雄性大鼠随机分为3组：对照组、DM组、DM+WXKL组。DM+WXKL组每日灌胃WXKL 3g/kg。8周后，超声心动图，血流动力学检查，组织学，电生理学研究，线粒体呼吸功能和蛋白质印迹法进行了评估。H2 O2处理导致原代心房成纤维细胞ROS增加，细胞内MMP和线粒体耗氧量降低。WXKL改进了上述变化。DM组大鼠心房纤维化程度加重，左房内径增大，心房传导速度减慢，传导不均一性增加，心房颤动诱发率增高，线粒体蛋白表达降低，DM+WXKL组除左房内径外，其他指标均得到改善。WXKL通过调节线粒体功能和内稳态，减少线粒体ROS，改善糖尿病大鼠心房重构。
Mitochondrial dysfunction and oxidative stress play an important role in the pathogenesis of both atrial fibrillation (AF) and diabetes mellitus (DM). Wenxin Keli (WXKL), an antiarrhythmic traditional Chinese medicine, has been shown to prevent cardiac arrhythmias through modulation of cardiac ion channels. This study tested the hypothesis that WXKL can improve atrial remodeling in diabetic rats by restoring mitochondrial function. Primary atrial fibroblasts of neonatal SD rats were divided into four groups: control, hydrogen peroxide (H2O2), H2O2+WXKL 1 g/L, and H2O2+WXKL 3 g/L groups. Intracellular mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitochondrial oxygen consumption were measured. SD male rats were randomly divided into three groups: control, DM, and DM+WXKL groups. Rats in the DM+WXKL group were treated with daily gavage of WXKL at 3 g/kg. After eight weeks, echocardiography, hemodynamic examination, histology, electrophysiology study, mitochondrial respiratory function, and western blots were assessed. H2O2 treatment led to increased ROS and decreased intracellular MMP and mitochondrial oxygen consumption in primary atrial fibroblasts. WXKL improved the above changes. DM rats showed increased atrial fibrosis, greater left atrial diameter, lower atrial conduction velocity, higher conduction heterogeneity, higher AF inducibility, and lower mitochondrial protein expression, and all these abnormal changes except for left atrial diameter were improved in the DM+WXKL group. WXKL improves atrial remodeling by regulating mitochondrial function and homeostasis and reducing mitochondrial ROS in diabetic rats.