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α-硫辛酸对高糖培养施万细胞线粒体凋亡通路的影响 预览

Protective Effects of Alpha Lipoic Acid on Schwann Cells Oxidative Injury and Mitochondrial Pathway Activation of Apoptosis Induced by High Glucose
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摘要 目的 探讨α-硫辛酸(alpha lipoic acid,ALA)对高糖培养施万细胞氧化应激损伤及线粒体凋亡通路的影响。方法 原代培养并纯化后的大鼠施万细胞为研究对象,分为正常组(5.6mmol/L葡萄糖培养基)、高糖组(50mmol/L葡萄糖培养基)、渗透压对照组(5.6mmol/L葡萄糖培养基+44.4mmol/L甘露醇),以及高糖内分别加入不同浓度ALA (50、100、200μmol/L)组。流式细胞术检测施万细胞活性氧(ROS)及线粒体膜电位水平,Tunnel法检测施万细胞凋亡率,Western blot法检测bcl-2、bax、cyto C、cleaved-caspase-3及cleaved-caspase-9的表达。结果 与正常组比较,高糖组施万细胞内ROS水平明显增高(P〈0.01),线粒体膜电位下降,bcl-2蛋白表达降低(P 〈0.01),bax蛋白的表达增加(P 〈0.01),cyto C从线粒体到胞质的释放增加,caspase-9、caspase-3的活化水平增高,细胞凋亡率明显增高(P〈0.01)。ALA降低高糖所致的施万细胞内ROS水平的增高(P〈0.01),提高了线粒体膜电位(P〈0.01),上调bcl-2蛋白的表达(P〈0.01),下调bax蛋白的表达(P 〈0.01),减少了cyto C从线粒体到胞质的释放(P〈0.01,P〈 0.05),降低了caspase-9及caspase-3的活化(P〈0.01),从而抑制了施万细胞凋亡。结论 ALA可以抑制高糖所致的施万细胞氧化应激损伤及线粒体凋亡通路的激活。 Objective To investigate the inhibitory effects of alpha lipoic acid(ALA) on the high glucose-induced Schwann cells (SCs) oxidative stress and apoptosis.Methods Primarily cultured SCs were divided into several groups including 5.6mmol/L of glucose as the control (con),osmotic control,50mmol/L of glucose as high glucose(HG)and HG in the presence of 50μmol/L, 100μmol/L, 200μmol/L ALA for 48 hrs. Intracellular ROS generation and mitochondrial transmembrane potential were detected by flow cytometry analysis,while the apoptotic cells were was detected by Tunnel method.Western blot were performed to analyze the expression levels of some important proteins,such as bcl-2, bax, cyto c,cleaved-caspase-9 and cleaved-caspase-3.Results The relative levels of intracellular ROS and mitochondrial depolarization of SCs in HG group were higher than the control(P〈0.01).The apoptotic cells in the HG group were markedly increased than the control(P〈0.01).Compared to the control group,treatment with HG down-regulated the bcl-2 levels and up-regulated the bax expression(P〈0.01). In addition,treatment with HG increased the release of cyto c from the mitochondria to cytosol,the activation of caspase-9 and caspase-3 in SCs(P〈0.01).Treatment with ALA inhibited the HG-induced oxidative stress by reducing ROS accumulation, mitochondrial depolarization and apoptosis in SCs(P〈0.01). ALA also mitigated the HG-induced down-regulation of bcl-2 and the up-regulation of bax(P〈0.01). Furthermore,treatment with ALA attenuated the HG-mediated the release of cyto c from the mitochondria to cytosol,activation of caspase-9 and caspase-3(P〈0.01).Conclusion ALA antagonized the HG-mediated oxidative stress and mitochondrial pathway activation apoptosis in SCs.
作者 汪麟 张哲 王瑞 夏欣欣 韩萍萍 孙连庆 Wang Lin, Zhang Zhe, Wang Rui, etal( Department of Traditional Chinese Medicine, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Shaanxi 710061, China)
出处 《医学研究杂志》 2017年第11期49-53,共5页 Journal of Medical Research
基金 国家自然科学基金资助项目(81673785) 陕西省自然科学基金资助项目(2014JM4118) 陕西省自然科学基础研究计划重点项目(2015JZ023)
关键词 高糖 氧化应激 凋亡 施万细胞 Α-硫辛酸 High glucose Oxidative stress Apoptosis Schwann cells Alpha lipoic acid
作者简介 通讯作者:孙连庆,副主任医师、硕士研究生导师,电子信箱:sunlianqing1@163.com
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