中国组织工程研究2017，Vol.21Issue(28)：4512-4517,6.DOI:10.3969/j.issn.2095-4344.2017.28.014
NOD样受体热蛋白结构域相关蛋白3炎性小体在低氧诱导骨骼肌线粒体损伤中的作用
Role of NOD-like receptor family, pyrin domain containing 3 inflammasome in the hypoxia-induced skeletal muscle mitochondrial dysfunction
摘要
Abstract
BACKGROUND:Whether NOD-like receptor family,pyrin domain containing 3 (NLRP3) inflammasome is involved in hypoxia-induced skeletal muscle mitochondrial dysfunction,and the underlying mechanism remain unclear.OBJECTIVE:To observe the effect of NLRP3 inflammasome inhibitor VX-765 on skeletal muscle mitochondrial function,and to explore the role of NLRP3 inflammasome in hypoxia-induced mitochondrial dysfunction.METHODS:Thirty Sprague-Dawley rats were randomly divided into three groups:normoxia,hypoxia,and hypoxia plus VX-765 groups.The rats in the hypoxia group were subjected to hypoxia exposure in normobaric hypoxic tent with 11.3％ O2.The hypoxia plus VX-765 group rats were given the intraperitoneal injection of VX-765 (50 mg/kg) daily.All of the interventions lasted for 4 weeks.RESULTS AND CONCLUSION:VX-765 in hypoxia markedly inhibited the expression of NLRP3 and apoptosis-associated speck-like protein,attenuated caspase-1 activity and interleukin-1β content,and suppressed mitochondrial H2O2 generation.In addition,VX-765 in hypoxia markedly enhanced the expression of mitochondrial peroxisome proliferator-activated receptor y coactivator 1-α and cyclooxygenase ⅣV,elevated mitochondrial membrane potent and ATP synthetase activity.These results indicate that hypoxia induces skeletal muscle dysfunction through activating NLRP3 inflammasome and impairing mitochondrial function.The hypoxia-induced mitochondrial dysfunction enhances reactive oxygen species generation and further triggers interleukin-1 β production via the NLRP3 inflammasome activation.In turn,interleukin-lβ further impairs mitochondrial function through suppresseing peroxisome proliferator-activated receptor y coactivator 1 o,resulting in a vicious circle between NLRP3 inflammasome activation and mitochondrial dysfunction.关键词
组织构建/组织工程/低氧/骨骼肌/NLRP3炎性小体/线粒体/氧化应激/过氧化物酶体增殖物激活受体γ辅激活因子1α/国家自然科学基金分类
医药卫生引用本文复制引用
张子怡,薄海,杨爽,袁瑶,张勇..NOD样受体热蛋白结构域相关蛋白3炎性小体在低氧诱导骨骼肌线粒体损伤中的作用[J].中国组织工程研究,2017,21(28):4512-4517,6.基金项目
国家自然科学基金(31571224,81370454,31110103919) （31571224,81370454,31110103919）
天津市自然科学基金(14JCZDJC36600) （14JCZDJC36600）
武警后勤学院研究基金(WHB201507) （WHB201507）
the National Natural Science Foundation of China,No.31571224,81370454,and 31110103919 （）
the Natural Science Foundation of Tianjin,No.14JCZDJC36600 （）
the Science Foundation of Logistics University of Chinese PAPF,No.WHB201507. （）
