【摘 要】
：
肌萎缩是长期困扰人类的疾病,包括废用性肌萎缩,去神经支配肌萎缩,饥饿导致的肌萎缩和恶质病导致的肌萎缩。研究证明Atrogin1,Murf都是肌肉特异性E3蛋白连接酶,在不同类型肌萎缩早期均有表达,参与蛋白泛素化降解过程,已经成为鉴定肌萎缩发生的标志基因。人们将这些在肌萎缩过程中发挥关键作用的基因称为肌萎缩基因,并认为他们控制了肌萎缩发生发展的全过程。目前对小鼠废用性肌萎缩的蛋白质组学研究较少,对小
【机 构】
：
中国航天员科研训练中心,航天医学基础与应用国家重点实验室 中国航天员科研训练中心,人因工程重点实验
【出 处】
：
中国空间科学学会空间生命专业委员会第二十届学术研讨会暨中国宇航学会航天医学工程与空间生物学专业委员会第四届学术研讨会
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肌萎缩是长期困扰人类的疾病,包括废用性肌萎缩,去神经支配肌萎缩,饥饿导致的肌萎缩和恶质病导致的肌萎缩。研究证明Atrogin1,Murf都是肌肉特异性E3蛋白连接酶,在不同类型肌萎缩早期均有表达,参与蛋白泛素化降解过程,已经成为鉴定肌萎缩发生的标志基因。人们将这些在肌萎缩过程中发挥关键作用的基因称为肌萎缩基因,并认为他们控制了肌萎缩发生发展的全过程。目前对小鼠废用性肌萎缩的蛋白质组学研究较少,对小鼠肌萎缩恢复早期比目鱼肌的蛋白质组学研究更是少有报道。而比目鱼肌是重要的抗重力肌,它在废用性肌萎缩中萎缩程度最大,具有重要的研究价值。但是由于体积小,取材困难,对肌萎缩及恢复期小鼠比目鱼肌的蛋白质组学一直少有研究,我们的研究旨在填补这项空缺。在本研究中,我们发现与对照组相比尾悬吊14天后小鼠比目鱼肌的重量和肌纤维的横截面积均显著下降,而恢复3天后比目鱼肌的重量和肌纤维的横截面积与对照组几无差别。利用蛋白双向电泳以及质谱等实验手段,我们初步筛选到21个与肌萎缩及肌萎缩恢复过程相关的差异蛋白,这些蛋白主要属于收缩蛋白、热休克蛋白、蛋白水解和代谢相关的蛋白。其中蛋白水解酶transthyretin在肌萎缩时表达显著上调,恢复时表达显著下降。热休克蛋白在肌萎缩时表达显著下调,恢复时表达显著上调。脂代谢相关蛋白fast-type MLC2在肌萎缩时表达显著上调,恢复时表达显著下降。同时我们还用定量PCR和Western blot的方法对部分蛋白的表达进行了验证。这些结果表明,尾悬吊导致的肌萎缩过程与蛋白水解的增加、代谢类型的转换、肌纤维类型的转换以及热休克蛋白表的紊乱等过程紧密相关。我们发现的差异蛋白可能在肌萎缩的发生以及恢复过程中发挥着重要作用,而这些差异蛋白的研究将为揭示废用性肌萎缩的发生机制提供重要的线索,为失重性肌萎缩的对抗和治疗提供重要理论依据。
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