不同运动方式对自然衰老小鼠自噬基因表达的影响及与Sarcopenia的关联

Effects of Different Exercises Type on Sarcopenia-Associated ATGS Expression in Skeletal Muscle of Natural Aging Mouse

目的:探讨终身跑台、爬梯训练对C57BL/6自然衰老小鼠Sarcopenia关联的自噬相关基因的影响,从而推测自噬在Sarcopenia发生发展中的作用,以及推测运动预防Sarcopenia的作用机理。方法:36只C57BL/6小鼠随机分为青年对照组(YC)、老年对照组(OC)、终身跑台组(LE)、终身爬梯组(LR),每组各9只,其中YC组为3月龄,其余各组自然生长至20月龄。LE组和LR组分别进行为期17个月的跑台和爬梯训练,利用实时荧光定量PCR的生物学方法检测自噬相关基因LC3、Beclin1、和LAMP-2 mRNA的表达。结果:1)C57BL/6自然衰老小鼠骨骼肌质量下降,出现严重Sarcopenia佂状。2)与YC组比较,OC组小鼠LC3b、LAMP-2b mRNA表达量显著升高,LC3a、Beclin1和LAMP-2a mRNA的变化无显著性差异。3)与OC组相比,终身耐力训练可使LC3a显著升高;使LC3b、Beclin1、LAMP-2a、LAMP-2b mRNA表达量显著降低。4)与OC组相比,终身抗阻训练可使LC3a、Beclin1、LAMP-2a mRNA表达量降低,但无显著性差异;使LC3b mRNA得表达量显著降低。5)与LE组相比,LR组Beclin1、LAMP-2a、LAMP-2b表达量升高,且具有极显著性差异。结论:1)20月龄C57BL/6小鼠符合Sarcopenia研究标准,可作为研究Sarcopenia的模式动物。2)20月龄C57BL/6小鼠腓肠肌巨自噬及CMA活性显著升高,可能造成细胞过度自噬造成蛋白质降解增加,进而诱导产生Sarcopenia。3)终身耐力运动可以有效抑制细胞过度自体吞噬,减少蛋白质降解,缓解Sarcopenia佂状。4)终身抗阻训练可在一定范围内降低自体吞噬活性,增加蛋白质合成,缓解Sarcopenia佂状。5)终身耐力训练控制骨骼肌过度自噬效果要优于终身抗阻训练。

Objective： This article is designed to determine the alterations of Autophagy in 20 -nlonths C57BL/6 skeletal muscle with Sareopenia, to observe the effect of a life-long endurance and resistance exercise on the Auto- phagy related to genes expression, and to provide some effective ways that can counterwork Sarcopenia for skeletal muscle. Methods： 36 C57BL/6 mice were randomly divided into young control group （YC） , older control group （OC） , life-long treadmill group （LE） , life-long ladder group （LR） , 9 mice for each group. The age of YC group mice were 3 months and other groups were raised naturally to 20 months. The LE and LR groups were engaged in a treadmill and ladder-climbing training for 17 months respectively. They did exercise once a day and three days a week. Then Real-Time PCR was used to detect the Autophagy related genes LC3, Beclinl a,ld LAMP -2 mRNA expression. Results ： 1 ） With the age growing, skeletal muscle mass decreased significantly in natural aging mice, and the Sarcopenia was occurred in these mice. 2） Compared with the YC group, LC3b, LAMP -2b mRNA ex- pressions were significantly increased in OC group, and LAMP - 2a mRNA expression wash ＇ t significautly changed. 3） Compared with the OC group, lifelong endurance training significantly increased the ratio of LC3a/ LC3b, and decreased Beclinl, LAMP -2a, LAMP -2b mRNA expression. 4） Compared with the OC group, life- long resistance training decreased LC3a, Beclinl, LAMP- 2a mRNA expression, but not significantly; and LC3b mRNA expression decreased significantly. 5） Compared with the LE group, the expressions of Beclinl, LAMP- 2a, LAMP -2b increased a lot. Conclusion： 1 ） 20 months old C57BL/6 mice can be used as the model animal of Sarcopenia. 2） With the age growing, the autophagy flux increased, protein degradation increased, then lead to Sarcopenia. 3 ） Lifelong endurance training can effectively inhibit excessive autophagy, thus ease Sarcopenia symp- toms. 4） Lifelong resistance training can reduce Autophagic activity and protein degradation in a certain range to prevent the development of sarcopenia. 5 ） Life-long endurance training had a better effect on the control of exces- sive autophagy than the life-long resistance training.