基础医学与临床 ›› 2018, Vol. 38 ›› Issue (7): 922-927.

• 研究论文 • 上一篇    下一篇

肌肉衰减综合征小鼠腓肠肌Sirt1和mTOR活性的变化

荆小马1,王全全2,郝延磊3   

  1. 1. 山东大学医学院
    2. .山东大学 齐鲁医学院
    3. 济宁医学院附属医院
  • 收稿日期:2017-12-20 修回日期:2018-03-27 出版日期:2018-07-05 发布日期:2018-06-29
  • 通讯作者: 郝延磊 E-mail:yanleihao301@live.com
  • 基金资助:
    mTOR和Sirt1在老年肌肉衰减综合征发病机制中的相互作用及其对线粒体功能的影响; Sirt1在老年肌肉衰减综合征和废用性肌萎缩病理生理机制中的作用

Alterations of Sirt1 and mTOR activities in mouse gastrocnemius muscle with sarcopenia

  • Received:2017-12-20 Revised:2018-03-27 Online:2018-07-05 Published:2018-06-29

摘要: 目的 观察肌肉衰减综合征小鼠腓肠肌Sirt1和mTOR活性的变化。方法 将雄性C57BL/6J老年(26月龄)和中年(6月龄)小鼠各16只分别随机分为2组,每组8只(n=8): 即中年对照(MC)组、中年后肢悬提(MS)组、老年对照(AC)组及老年后肢悬提(AS)组。老年小鼠后肢悬提(HLS) 2周建立肌肉衰减综合征小鼠模型,试剂盒和蛋白免疫印迹分别测定Sirt1和mTOR信号转导通路相关因子及蛋白的表达。结果 1)、NAD+含量和NAD+/NADH比率:AC组明显低于MC组(P<0.01,P<0.05),HLS组显著少于对照组(P<0.01,P<0.05)。2)、Sirt1表达:AC组明显高于MC组(P<0.05),HLS组显著高于对照组(P<0.05)。3)、Sirt1下游底物表达(PGC-1α、FOXO1和P53)、与衰老相关的NAMPT蛋白表达和Sirt1活性:AC组明显低于MC组(P<0.05,P<0.05,P<0.01),HLS组显著少于对照组(P均<0.05)。4)、磷酸化的mTOR、p70S6K和4E-BP1:AC组明显高于MC组(P<0.05),HLS组显著少于对照组(P<0.05)。结论 Sirt1和mTOR参与了肌肉衰减综合征小鼠的发病。

关键词: 肌肉衰减综合征, Sirt1, mTOR

Abstract: Objective To observe the alterations of Sirt1 and mTOR activity in gastrocnemius muscles of mice with sarcopenia. Methods aged (26 months old) and young (6 months old) male C57BL/6J mice (n=16,respectively) were randomly arranged into 2 groups respectively,n=8 in each group: middle-aged control(MC), middle-aged suspension(MS), aged control(AC) and aged suspension(AS). Aged mice were hindlimb suspended for two weeks to establish a sarcopenic model. Kits and Western blot were used to determine related factors and protein expression of Sirt1 and mTOR pathway. Results 1.the content of NAD+ and the ratio of NAD+/NADH: AC group was significantly lower than MC group (P<0.01 or P<0.05), HLS group was significantly less than the control group (P<0.01 or P<0.05). 2. Sirt1 expression: AC group were significantly higher than MC group (P<0.05), and HLS group was significantly higher than that of the control group (P<0.05).3. Sirt1 downstream substrates (PGC-1α, FOXO1 and P53), NAMPT protein expression and Sirt1 activity: AC group was significantly lower than MC group (P<0.05 or P<0.05 or P<0.01), HLS group was significantly less than the control group (P<0.05 or P<0.05 or P<0.05). 4. phosphorylation of mTOR, p70S6K and 4E-BP1: AC group was significantly higher than MC group (P<0.05), HLS group was significantly less than the control group (P<0.05). Conclusions Sirt1 and mTOR are involved in the pathogenesis of mice with sarcopenia.

Key words: Sarcopenia, Sirt1, mTOR