Objective: To detect the expression of SIRT1 and Ac-FOXO1 in rats after endurance training and acute exhaustive exercise, and explicit the myocardial protective effect of SIRT1. Methods: Rats were randomly divided into four groups: control group(n=20), exhaustive exercise group (E group, n=20), exhaustive exercise group + endurance training (TE group, n=18), exhaustive exercise group + endurance training + selective SIRT1 inhibitor (TSE group, n=17). The Control and E groups were fed routinely for 5 weeks. The TE and TSE groups were subjected to swimming exercise for 5 weeks for endurance exercising. The TSE group was intraperitoneally injected with selective SIRT1 inhibitor Sirtinol(2 mg/kg) at 30 minutes before endurance exercising. The E, TE and TSE groups were subjected to exhaustive exercise. The myocardial tissues of rats were collected after exhaustive exercise. Real-time polymerase chain reaction (PCR) and Western blot analysis were performed to detect the myocardial mRNA and protein expressions of SIRT1 and Ac-FOXO1. The myocardial protein expression of Bax and Bcl-2 was also detected by Western blot. Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay was used to assess the apoptosis of myocardial cells. Results: Compared with Control group, the SIRT1 and Bcl-2 expression in the myocardial tissue was obviously decreased, while the Ac-FOXO1, Bax, and the myocardial cell apoptosis were significantly increased in E group (all P<0.01). Compared with E group, the expression of SIRT1 and Bcl-2 was obviously up-regulated (both P<0.01), while the Ac-FOXO, Bax and the myocardial cell apoptosis was significantly reduced in TE group (all P<0.01). Compared with TE group, the SIRT1 and Bcl-2 expression was obviously lower (both P<0.01), while Ac-FOXO1, Bax, and the cell apoptosis were significantly higher in group TSE (all P<0.01). Conclusion: Endurance training could protect myocardium by reducing the myocardial oxidative stress injury and apoptosis via activating SIRT1 signaling pathway, up-regulating the myocardial expression of SIRT1 and regulating the deacetylation of FOXO1.
目的： 观察力竭运动模型大鼠耐力运动训练后心脏沉默信息转录调控因子1(SIRT1)、乙酰化叉头转录因子1(Ac-FOXO1)的表达变化，探讨耐力运动训练心肌保护的作用机制。 方法： 将雄性Wistar大鼠按完全随机法分为4组，即对照组(n＝20)、力竭运动组(力竭组，n＝20)、耐力运动训练＋力竭运动组(TE组，n＝18)、耐力运动训练＋Sirtinol(选择性SIRT1抑制剂)＋力竭运动组(TSE组，n＝17)。对照组和力竭组大鼠常规饲养5周。TE组和TSE组大鼠进行5周耐力运动训练(游泳)，TSE组大鼠运动前30 min腹腔注射Sirtinol(2 mg/kg)。5周后，力竭组、TE组和TSE组大鼠各进行一次性力竭游泳运动。于力竭运动后留取各组大鼠心肌组织，分别采用实时荧光定量逆转录聚合酶链反应及Western blot法检测心肌SIRT1 mRNA和蛋白表达，Western blot法检测心肌Ac-FOXO1、抗凋亡蛋白Bcl-2和促凋亡蛋白Bax的表达，TUNEL法检测心肌细胞凋亡指数。 结果： (1)各组大鼠心肌组织SIRT1 mRNA和蛋白表达：力竭组大鼠心肌组织SIRT1 mRNA表达水平明显低于对照组(P<0.01)，TE组则明显高于力竭组(P<0.01)，TSE组又明显低于TE组(P<0.01)。力竭组大鼠心肌组织SIRT1蛋白表达水平明显低于对照组(P<0.01)，TE组则明显高于力竭组(P<0.01)，TSE组又明显低于TE组(P<0.01)。(2)各组大鼠心肌组织Ac-FOXO1、Bcl-2和Bax的蛋白表达：力竭组大鼠心肌组织Bcl-2表达水平明显低于对照组(P<0.01)，Ac-FOXO1和Bax则均明显高于对照组(P均<0.01)。TE组大鼠心肌组织Bcl-2蛋白表达水平则明显高于力竭组(P<0.01)，Ac-FOXO1和Bax均明显低于力竭组(P均<0.01)。TSE组大鼠心肌组织Bcl-2蛋白表达水平又明显低于TE组(P<0.01)，Ac-FOXO1和Bax均明显高于TE组(P均<0.01)。(3)各组大鼠心肌细胞凋亡指数：力竭组大鼠心肌细胞凋亡指数明显大于对照组[(42.10±1.47)%比(17.31±1.32)%，P<0.01]，TE组[(15.69±1.81)%]则明显小于力竭组(P<0.01)，而TSE组[(35.34±1.36)%]又明显大于TE组(P<0.01)。 结论： 耐力运动训练可以激活大鼠心脏SIRT1信号通路，上调SIRT1的表达，调节FOXO1的去乙酰化水平，抑制心肌细胞凋亡，从而发挥心肌保护作用。.
Keywords: Apoptosis; Myocardium; Resistance training.