规律运动对增龄大鼠比目鱼肌细胞凋亡与自噬及PGC-1α信号调控的影响  

The Effects of Regular Aerobic Exercise on Soleus Apoptosis and Autophagy as well as PGC-1α Signal Regulation of Aging Rats

作　　者：刘文锋[1,2] 魏霞[1] 张冰侠 印大中[1,2] 汤长发[1] 唐利花 陈宗平[1] Liu Wenfeng Wei Xia Zhang Bingxia Yin Dazhong Tang Changfa Tang Lihua Chen Zongping(Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha 410081, China)

机构地区：[1]湖南师范大学体适能与运动康复湖南省重点实验室,湖南长沙410012 [2]湖南师范大学蛋白质化学与发育生物学教育部重点实验室,湖南长沙410081

出　　处：《中国运动医学杂志》2017年第2期128-135,共8页Chinese Journal of Sports Medicine

基　　金：国家自然科学基金(31271257);国家高科技863计划(2008AA02Z411);湖南省自然科学基金(11JJ6082和14JJ7035);湖南教育厅优秀青年基金(12B088);湖南师范大学青年优秀人才培养计划(ET1507)共同资助

摘　　要：目的:探讨规律性运动对骨骼肌肌纤维增龄性老化过程中的细胞凋亡与细胞自噬及PGC-1α信号调控的作用机制。方法:选用SPF级健康雄性3月龄(青年,n=20)、13月龄(中年,n=24)和22月龄(老年,n=24)大鼠,按体重随机分为青年对照组(Y-SED)、青年运动组(Y-EX);中年对照组(M-SED)、中年运动组(M-EX);老年对照组(O-SED)和老年运动组(O-EX)。对照组3组静息,运动组3组实施10周规律的递增负荷中等强度有氧运动。采用HE染色检测肌纤维纵横两个面的形态学变化,免疫印迹法检测SOD表达水平、TUNEL法检测凋亡,免疫印迹法等检测自噬及PGC-1α通路的蛋白质表达水平。结果:(1)HE染色显示规律有氧运动提高了增龄性大鼠比目鱼肌肌纤维的成束性和紧密性,而免疫印迹结果显示其提高了SOD表达水平。(2)各年龄对照组大鼠比目鱼肌细胞凋亡的增加呈现增龄性趋势,而规律有氧运动各年龄大鼠凋亡指数分别增加了7.55%、20.26%(Ρ<0.05)和14.52%(Ρ<0.05)。(3)各年龄对照组大鼠自噬基因LC-Ⅲ呈现增龄性降低趋势,规律有氧运动各年龄大鼠的LC-Ⅲ均显著上升(Ρ<0.01),各年龄运动组自身LC-Ⅲ却呈现增龄性上升趋势。(4)与相对应的对照组相比较,规律有氧运动各年龄大鼠自噬因子Beclin1表达均显著上升(Ρ<0.05),其中Y-EX组上升最显著(Ρ<0.01),各年龄运动组自身Be-clin1的表达水平却呈现增龄性降低趋势。(5)与Y-SED组相比,M-SED组的PGC-1α表达水平增加,但O-SED组比Y-SED和M-SED两组的PGC-1α表达水平显著下降(Ρ<0.01)。与安静对照组相比较,Y-EX和M-EX两组PGC-1α表达水平均呈现上升趋势,其中与O-SED组相比,O-EX组PGC-1α表达水平显著上升(Ρ<0.01,Ρ<0.05)。结论:自噬与凋亡两者之间的平衡稳定关系影响着比目鱼肌增龄性老化的发生发展,规律有氧运动对增龄性老化大鼠比目鱼肌细胞自噬与凋亡的影响出现增龄性变化,其机制是通过激发BeclinObjective To explore the effect of regular aerobic exercises on soleus apoptosis and au-tophagy as well as PGC-1 alpha（PGC-1α） signal regulation in aging rats. Methods In this study,3-month-old,13-month-old and 22-month-old specific pathogen free（SPF） male Sprague-Dawley（SD）rats were randomly divided into a young（Y-SED）, a middle-aged（M-SED） and an old-aged（O-SED）sedentary control group,and the corresponding young, middle-aged and old-aged aerobic exercise（Y-EX,M-EX and O-EX） groups. The 10-week regular moderate-intensity aerobic exercise interventionwith progressive intensity was carried out in the EX groups, while the control groups were not givenany intervention. Haematoxylin and easin（HE） staining was used to observe the morphological changesof muscular fibers horizontally and vertically. Western blotting was performed to decide the expressionof superoxide dismutase（SOD）, screen and verify the related signal pathways for the autophagy andapoptosis. TUNEL assay was used to measure apoptosis. Results The regular aerobic exercise significant-ly improved the bundling and density of soleus muscle fibers, as well as the SOD expression. In con-trol groups apoptosis increased as the age increased, while that of Y-EX,M-EX and O-EX groups in-creased by 7.55% and 20.26%（Ρ 0.05） and 14.52%（Ρ 0.05） respectively. The LC- Ⅲ autophagygene reduced with age in each sedentary group,but increased significantly（Ρ0.01） in regular aerobicexercise rats with age. Compared with the corresponding control groups,the expression of autophagy fac-tor Beclin1 increased significantly in EX groups（Ρ 0.05）, with most significant increase in Y- EXgroup. Compared with Y- SED group,the average expression of PGC- 1 alpha in M- SED group in-creased,but that of O- SED group decreased significantly（Ρ 0.01）compared to Y- SED and M- SEDgroups. Compared with the sedentary control groups,the average PGC-1 alpha expression in the groupY-EX and M-EX increased; but compared with O-SED group,tha

关 键 词：规律有氧运动 细胞凋亡 细胞自噬 过氧化物酶体增殖物激活受体γ辅激活因子1α 

分 类 号：R87[医药卫生—运动医学]