内源性二氧化硫通过次磺酸修饰NF-kappa B p65抑制TNF-alpha诱导的脂肪细胞炎症

项目名称： 内源性二氧化硫通过次磺酸修饰NF-kappa B p65抑制TNF-alpha诱导的脂肪细胞炎症

项目编号： No.81500672

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张恒

作者单位： 首都医科大学

项目金额： 18万元

中文摘要： 脂肪组织慢性炎症与胰岛素抵抗及肥胖发生密切相关。二氧化硫是新近发现的内源性气体信号分子，具有重要的代谢生物学作用。然而脂肪细胞是否存在内源性二氧化硫及其生成体系、脂肪细胞来源的二氧化硫调节对脂肪细胞炎症反应的调节作用和机制，目前尚不清楚。本研究预实验结果提示，脂肪组织存在内源性二氧化硫及其生成体系。本研究拟探索脂肪内源性二氧化硫及其生成体系；采用给予二氧化硫供体、二氧化硫生成酶抑制剂或基因干预的方法，研究脂肪内源性二氧化硫对肿瘤坏死因子诱导的脂肪细胞炎症因子表达和分泌的调节作用；以NF-kappa B信号途径为切入点，揭示内源性二氧化硫调节脂肪细胞炎症的信号通路；以NF-kappa B p65第38位半胱氨酸巯基基团次磺酸修饰为靶点，研究二氧化硫抑制脂肪细胞炎症过程中NF-kappa B信号通路的分子机制。以期阐明内源性二氧化硫对脂肪细胞炎症反应的调节作用及具体机制。

中文关键词： 二氧化硫；脂肪细胞；炎症；肥胖；胰岛素抵抗

英文摘要： Adipose chronic inflammation is closely associated with insulin resistance and obesity. Sulfur dioxide is a newly discovered gaseous signaling molecule which plays an important role in metabolism biology. However, whether endogenous sulfur dioxide generation system exists in adipocytes and how adipocytes-derived sulfur dioxide regulates adipose inflammation have been unclear. Our previous study indicated endogenous sulfur dioxide and its generation system existed in different adipose tissues of rat. The study is designed to investigate the existence of endogenous sulfur dioxide and its generation system in adipose; By using sulfur dioxide donor or endogenous sulfur dioxide production inhibitor or gene manipulation, the study is also designed to elucidate the regulatory effect of endogenous sulfur dioxide on inflammation in adipocytes. Furthermore, targeting on NF-kappa B pathway, the study aims to discover the signaling pathway by which sulfur dioxide improves inflammation in adipocytes. Meanwhile, focusing on the NF-kappa B p65 cysteine 38 thiol group, the study aims to examine the molecular mechanism by which endogenous sulfur dioxide suppresses NF-kappa B signaling pathway during adipocytes inflammation. These findings would deepening the understanding of the regulatory effect of endogenous sulfur dioxide on inflammation in adipocytes and its mechanism .

英文关键词： sulfur dioxide ;adipocytes;inflammation;obesity;insulin resistance