Irisin improves endothelial function in type 2 diabetes through reducing oxidative/nitrative stresses
Irisin improves endothelial function in type 2 diabetes through reducing oxidative/nitrative stresses
复制标题
鸢尾素通过减少氧化/硝化应激来改善 2 型糖尿病的内皮功能。
DOI：
10.1016/j.yjmcc.2015.07.015
复制
发表时间：
2015-10-01
影响因子：
5
通讯作者：
Tao, Ling
中科院分区：
文献类型：
--
作者：
Zhu, Di;Wang, Haichang;Tao, Ling
血管并发症是糖尿病患者死亡的主要原因，而血管内皮功能障碍是糖尿病血管并发症中最早发生的事件。据报道，2型糖尿病患者的血浆鸢尾素水平显著降低。本研究旨在探讨鸢尾素是否改善2型糖尿病患者的内皮功能及其机制。采用高脂饲料喂养C57 BL/6小鼠建立2型糖尿病模型。2型糖尿病小鼠表现出血清鸢尾素水平降低和内皮功能受损。基于内皮依赖性血管舒张和p-VASP水平的评价，鸢尾素治疗（0.5 mg/kg/d）两周改善了血管功能。为了研究鸢尾素的直接内皮保护作用，将糖尿病主动脉节段与鸢尾素（1 mg/ml）离体孵育。暴露于鸢尾素改善了糖尿病血管的内皮依赖性血管舒张。在机械方面，糖尿病主动脉节段表现出增加的氧化/硝化应力。Irisin减少糖尿病诱导的氧化/硝化应激，通过减少超氧化物和过氧亚硝酸盐的过度产生以及iNOS和gp 91（phox）的下调来证明。为进一步研究鸢尾素对内皮细胞的保护作用及其机制，采用高糖高脂（HG/HF）培养的人脐静脉内皮细胞（HUVECs）与鸢尾素预孵育。Irisin（1 μ g/ml）可能通过抑制PKC-β/NADPH氧化酶和NF-κ B B/iNOS通路的活化，减轻HG/HF诱导的HUVECs氧化/硝化应激和凋亡。综上所述，鸢尾素通过抑制涉及PKC-β/NADPH氧化酶和NF-κ B/iNOS的信号通路，部分地通过减少氧化/硝化应激来减轻2型糖尿病的内皮功能障碍，这表明鸢尾素可能是治疗糖尿病血管并发症的有希望的分子。(C)2015爱思唯尔有限公司版权所有。
Vascular complications are the major causes of death in patients with diabetes, and endothelial dysfunction is the earliest event in vascular complications of diabetes. It has been reported that plasma irisin level is significantly reduced in patients with type 2 diabetic patients. The present study aimed to investigate whether irisin improved endothelial function in type 2 diabetes as well as the underlying mechanisms. The type 2 diabetes model was established by feeding C57BL/6 mice with high-fat diet. The type 2 diabetic mice exhibited reduced serum irisin level and impaired endothelial function. Irisin treatment (0.5 mg/kg/d) for two weeks improved vascular function based on the evaluation of endothelium-dependent vasorelaxation and p-VASP levels. To investigate the direct endothelial protective effects of irisin, diabetic aortic segments were incubated with irisin (1 mg/ml) ex vivo. Exposure to irisin improved endothelium-dependent vasorelaxation of diabetic aortas. Mechanically, the diabetic aortic segments exhibited increased oxidative/nitrative stresses. Irisin reduced the diabetes-induced oxidative/nitrative stresses evidenced by reducing overproduction of superoxide and peroxynitrite, and down-regulation of iNOS and gp91(phox). To further investigate the protective effects of irisin on endothelial cells and the underlying mechanisms, human umbilical vein endothelial cells (HUVECs) cultured in high-glucose/high-fat (HG/HF) medium were pre-incubated with irisin. Irisin (1 mu g/ml) reduced the oxidative/nitrative stresses and apoptosis induced by HG/HF in HUVECs probably via inhibiting activation of PKC-beta/NADPH oxidase and NF-kappa B/iNOS pathways. Taken together, irisin alleviates endothelial dysfunction in type 2 diabetes partially via reducing oxidative/nitrative stresses through inhibiting signaling pathways implicating PKC-beta/NADPH oxidase and NF-kappa B/iNOS, suggesting that irisin may be a promising molecule for the treatment of vascular complications of diabetes. (C) 2015 Elsevier Ltd. All rights reserved.