α-硫辛酸抑制慢性低氧大鼠骨骼肌线粒体的氧化应激  

Alpha-lipoic acid inhibits mitochondrial oxidative stress in the rat skeletal muscle with chronic hypoxia exposure

作　　者：肖频[1,2] 庞奕辉[3] 彭朋[1] 薄海[1] 

机构地区：[1]武警后勤学院军事训练医学教研室,天津市300162 [2]武警江西总队医院药剂科,江西省南昌市330001 [3]武警后勤学院远程继续教育处,天津市300162

出　　处：《中国组织工程研究》2013年第28期5216-5222,共7页Chinese Journal of Tissue Engineering Research

基　　金：天津市应用基础及前沿技术研究计划青年基金项目(12JCQNJC07900);武警后勤学院博士启动基金(WYB201106)~~

摘　　要：背景:α-硫辛酸被誉为"全能抗氧化剂"和"线粒体营养剂",但其是否可用于慢性低氧骨骼肌的防护,及其相关机制尚不清楚。目的:观察α-硫辛酸对慢性低氧大鼠骨骼肌线粒体活性氧生成及抗氧化酶系的作用,并探讨α-硫辛酸作用的相关信号通路。方法:将36只SD大鼠随机分为常氧对照组、单纯低氧组和单纯低氧+α-硫辛酸组。低氧干预为常压低氧帐篷,氧体积分数设定为11.3%;α-硫辛酸干预为标准饲料中添加α-硫辛酸(0.25%)。各种干预均持续4周。结果与结论:α-硫辛酸显著上调Sirtuin-3表达,提高线粒体ATP合成活力和膜电位,上调线粒体态3呼吸速率、呼吸控制比和磷氧比,下调态4呼吸速率,促进并上调锰超氧化物歧化酶、谷胱甘肽过氧化物酶、过氧化氢酶等线粒体抗氧化酶系活性,从而抑制线粒体H2O2产生速率,降低线粒体丙二醛含量。表明α-硫辛酸可提高慢性低氧骨骼肌线粒体能量代谢效率,抑制活性氧生成。并通过提高线粒体抗氧化酶系活性,抑制低氧诱导的氧化应激。α-硫辛酸对低氧骨骼肌线粒体的保护效应可能与其上调态3呼吸速率有关。METHODS： Thirty-six Sprague Dawley rats were randomly divided into three groups： normoxia control group, hypoxia control group, and hypoxia＋α-lipoic acid group. Rats in the hypoxia control group were subjected to hypoxia exposure in normobaric hypoxic tent with 11.3% oxygen concentration. Rats in the hypoxia＋α-lipoic acid group were induced by adding a-lipoic acid （0.25%） in the normal diet. All the interventions were lasted for 4 weeks. RESULTS AND CONCLUSION： a-lipoic acid in hypoxia could markedly enhance the mitochondrial Sirtuin-3 expression, improve the mitochondrial adenosine triphosphate synthesis activity and membrane potential, up-regulate the mitochondrial state 3 respiratory rate, respiratory control ratio and ratio of phosphorus to oxygen, down-regulate the mitochondrial state 4 respiratory rate and promote and up-regulate the activity of mitochondrial antioxidant enzymes such as manganese superoxide dismutase, glutathione peroxidase and catalase, thus inhibiting mitochondrial H202 generation rate and reducing mitochondrial malondialdehyde level. The results indicated that α-lipoic acid could improve the efficiency of energy metabolism of chronic hypoxia skeletal muscle mitochondria and inhibit reactive oxygen generation, and it could inhibit the oxidative stress through improvingantioxidant enzyme activity of mitochondria. The protection mechanism of a-lipoic acid on hypoxia skeletal muscle mitochondria may be related to the increasing of mitochondrial state 3 respiratory rate.

关 键 词：组织构建 组织构建细胞学实验 肌肉肌腱韧带 慢性低氧 Α-硫辛酸 线粒体 Sirtuin-3 氧化应激 骨骼肌 省级基金 

分 类 号：R318[医药卫生—生物医学工程]