孕哺期磺胺间甲氧嘧啶暴露对mTOR介导仔鼠骨骼肌蛋白合成通路的影响

项目名称： 孕哺期磺胺间甲氧嘧啶暴露对mTOR介导仔鼠骨骼肌蛋白合成通路的影响

项目编号： No.81202209

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 刘开永

作者单位： 安徽医科大学

项目金额： 23万元

中文摘要： 磺胺间甲氧嘧啶可降低小鼠骨骼肌蛋白的含量。mTOR(雷帕霉素靶蛋白)是公认的介导骨骼肌蛋白合成的关键信号，尽管磺胺类要兽药能引起机体甲状腺素水平降低，但是对其调控蛋白质合成异常的信号通路尚未阐明。因此，我们推测磺胺间甲氧嘧啶可能是通过影响mTOR为核心信号通路的调控作用致使仔鼠骨骼肌蛋白合成异常。为了证实这一假说， 本课题拟采用分子生物学、高效液相色谱-质谱串联分析技术，从分子到整体两个层次，对孕哺期大鼠暴露该药后，依据母鼠IGF-I、胰岛素、甲状腺激素水平和仔鼠骨骼肌IGF-I水平，结合暴露剂量，发现PI3K/Akt/mTOR 及 mTOR/p70S6K、4E-BP1相关信号通路影响仔鼠骨骼肌蛋白合成异常的分子机理。本课题将从新的视角阐明磺胺间甲氧嘧啶影响mTOR介导仔鼠骨骼肌蛋白合成的通路，为生命早期磺胺类兽药暴露的危害风险评估提供理论和实验依据。

中文关键词： mTOR；骨骼肌；海马；短链脂肪酸；磺胺间甲氧嘧啶

英文摘要： Sulfamonomethoxine can reduce the protein content of mouse skeletal muscle. The mammalian TOR (mTOR) is recognized a principal regulator of protein synthesis in skeletal muscle, Sulfonamides can cause the body's thyroid hormone levels lower, but the signaling pathway mediated by mTOR in regulation of abnormal protein synthesis has not been elucidated.Therefore, we speculate sulfamonomethoxine may affect mTOR signaling pathway resulting in abnormalities of protein synthesis in offspring skeletal muscle. To verify the hypothesis, molecular biology and high performance liquid chromatography - mass spectrometry techniques are used, from the molecular to the whole levels, the rats in pregnaney and lactation were exposed to the drug, according to IGF-I,insulin, thyroid hormone levels in the mother rat and IGF-I levels in skeletal muscle of offspring rats, combined with the exposure dose, the PI3K/Akt/mTOR and mTOR/p70S6K, the 4E-BP1 signaling pathways ,including the molecular mechanism,will be found influencing the skeletal muscle protein synthesis abnormally in offspring rats . This topic from a new perspective will clarify the molecular mechanism of abnormal protein synthesis in offsprings skeletalmuscle, exposed to sulfamonomethoxine ,via mTOR-mediated pathway, and the results will provide theoretical and experi

英文关键词： mTOR；Skeletal Muscle；Hippocampus；short chain fatty acids；sulfamonomethoxine