跑台运动对Sarcopeniadx鼠Caspase依赖与非依赖性细胞凋亡基因mRNA表达的影响

摘要

目的:探讨跑台运动对Sarcopenia/b鼠骨骼肌线粒体介导Caspase依赖与非依赖性细胞凋亡信号通路中凋亡基因mRNA的影响.方法:以30只快速老化小鼠(SAMP8)为研究对象,将其分为青年安静组(YC组,12周龄)、老年安静组(OC组,29周龄)和老年跑台运动组(OE组,29周龄),每组10只.OE组适应性饲养l周后开始跑台运动,每天1次,每周运动5天,持续8周,末次训练结束后24～呐48 h内将3组小鼠分别断头处死取腓肠肌,以小鼠腓肠肌质量(mg)除以对应体重(g)求得Sarcopenia Index(SI).采用实时荧光定量PCR方法,分别检测各组腓肠肌Caspase依赖性凋亡通路相关基因(Cyt C、apaf-1、Caspase-9和Caspase-3)和Caspase非依赖性凋亡通路相关基因(PARP、AIF和Endo G)mRNA表达.结果:(1)OC组腓肠肌SI值显著低于YC组,OE组SI值与OC组比较未见显著性差异.(2)与YC组相比,OC组腓肠肌apaf-1、Caspase-3和PARP mRNA表达均显著上调,AIF mRNA表达显著下调,而Cyt C、Caspase-9和Endo GmRNA表达未见显著变化.(3)与OC组相比,OE组腓肠肌Cyt C和AIF mRNA表达显著上调,Caspase-3和PARP mRNA表达显著下调,而apaf-1、Caspase-9和Endo G mRNA未见显著变化.结论:与Caspase非依赖性凋亡途径相比,Caspase依赖性凋亡途径在Sarcopenia发生中发挥更重要的作用;跑台运动一定程度上弱化衰老骨骼肌Caspase依赖性凋亡通路的促凋亡基mRNA表达,但对AIF诱导的Caspase非依赖性凋亡基因mRNA表达却呈现上调作用.%Objective To investigate the effect of treadmill running on the apoptotic genes mRNA in the skeletal mitochondria mediated caspase dependent and independent apoptotic signaling pathway of sarcopenia in mice. Methods Thirty male SAMP8 mice are selected as the aging model, together with the young control group (YC, 12w, n = 10) , old control group (OC, 29w, n = 10) and old endurance exercise group (OE, 29w, n = 10) . After one-week adaptive feeding, rats in group OE were forced to nm on treadmill with the frequency of 5 times per week for 8 weeks. The animals in each group were executed 24 to 48 hours after the last running, and sarcopenia Index (SI) was calculated by the ratio of gastrocnemius muscle mass (mg) to body weight (g). Real-time PCR was used to detect the changes in apoptotic genes, such as Cyt C, apaf-l, caspase-9, caspase-3, PARP, AIF and Endo G in each group. Results ( 1 ) The SI value of gastrocnemius in group OC was significantly lower than that in group YC, while no significant difference were observed between group OE and group OC.(2) Comparing to group YC, the expression of apaf-1, caspase-3 and PARP mRNA increased significantly, the expression of AIF mRNA decreased significantly, whereas Cyt C, caspase-9 and Endo G mRNA remained unchanged in group OC. (3) As compared to group OC, the expression of Cyt C and AIF mRNA increased significantly, and the expressions of caspase-3 and PARP mRNA decreased significantly with no difference in f apaf- 1, caspase-9 and Endo G mRNA in group OE. Conclusion As compared to caspase independent apoptotic signaling pathway, caspase dependent apoptotic signaling pathway plays more important role in the development of sarcopenia. Treadmill running exercise can attenuate the inclination of the apoptosis to some extent mediated by caspase dependent pathway in the senile mice, while the AIF induced caspase independent mRNA expression reveals up regulation.