失重性肌萎缩对小鼠运动耐力的影响及机制研究

来源 :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 | 被引量 : 0次 | 上传用户:Taosnowball
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  失重环境下,哺乳动物骨骼肌发生明显萎缩并伴有骨骼肌收缩特性和生理功能的改变,但失重性肌萎缩对骨骼肌运动耐力的影响及具体机制尚不清楚,本研究聚焦不同程度失重性肌萎缩的发生是否对运动耐力产生影响,并探讨其分子机制.将7周龄健康雄性C57BL6小鼠,随机分为地面对照组、尾悬吊7天、14天、28天组(n=7).28天后,各组小鼠以15m/min在小鼠跑台匀速运动,运动时使用电刺激,直至小鼠耗竭,测定各组小鼠运动时间和距离以研究失重性肌萎缩对运动耐力的影响;通过组织学、Western blot和免疫组织化学等方法,对比观察骨骼肌纤维的横截面积、Troponin I-SS和Troponin I-FS蛋白表达和慢肌纤维和快肌纤维含量的变化,研究失重性肌萎缩影响运动耐力的分子机制.结果表明: 1)与对照组相比,尾悬吊7天、14天、28天组小鼠运动耐力分别下降至对照组的69.8%、34.5%、28.3%;2)在失重性肌萎缩形成过程中,小鼠背侧腓肠肌、比目鱼肌和跖肌肌肉重量持续丢失;3)HE染色结果表明,尾悬吊7天后,腓肠肌、比目鱼肌和跖肌肌纤维横截面积明显减少,至14天后萎缩程度最大,但至28天后肌纤维横截面积略微增加,但同地面对照相比仍明显减少;4)Western blot和免疫组织化学结果表明,在失重性肌萎缩形成过程中,腓肠肌、比目鱼肌和跖肌中的Troponin I-SS含量下降,而Troponin I-FS含量增多.以上结果表明,在失重性肌萎缩形成过程中,小鼠的运动耐力持续下降,但在失重性肌萎缩形成前期,运动耐力的下降可能与肌纤维萎缩的相关性更高,伴随尾悬吊时间的延长,运动耐力的下降可能与Troponin I-SS的减少有关.
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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