游泳运动预处理抑制钙蛋白酶活性减轻心肌细胞膜的缺血-再灌注损伤

Swimming exercise preconditioning inhibits calpain activity and protects cardiomyocyte membrane against ischemia/reperfusion injury

目的探讨游泳运动预处理膜保护效应,以及钙蛋白酶在其中的作用。方法雄性SD大鼠先随机分为对照组和运动预处理组。8周游泳运动预处理结束后,在体心脏接受40 min缺血,2 h再灌注处理。对照组再随机分为假手术组、缺血-再灌注组和钙蛋白酶抑制剂MDL28170(3 mg/kg)干预组。结果与假手术组相比,缺血-再灌注组左心室收缩压峰值、左心室最大收缩速率与舒张速率和平均动脉压均降低,给予MDL28170和运动预处理则逆转缺血-再灌注的损伤作用。缺血-再灌注不仅增加钙蛋白酶的底物α-胞衬蛋白的水解和细胞膜钙蛋白酶催化亚基calpain1的募集,还破损细胞膜,使细胞内伊文思蓝的蓄积和膜骨架分子肌萎缩蛋白的丢失增加。尤为重要的是,这些现象在给予MDL28170和运动预处理后均明显减弱。结论运动预处理减轻心肌细胞膜的缺血-再灌注损伤,其作用与抑制钙蛋白酶的活性有关。

Objective To determine the protective effects of swimming exercise preconditioning on cardiomyocyte membrane and the role of calpain in this scenario. Methods SD male rats were randomly divided into control group and swimming exercise preconditioning group. The rats in the swimming exercise preconditioning group were subjected to 40 min cardiac ischemia and 2 h reperfusion after 8-week swimming exercise, whereas the rats in the control group were randomly allocated to receiving sham treatment, ischemia/reperfusion, or ischemia/reperfusion with MDL28170(3 mg/kg), an inhibitor of calpain. Results Compared with the sham group, ischemia/reperfusion weakened heart function, manifested as decreases in the peak value of left ventricular systolic pressure, the peak positive and negative rates of left ventricular pressure, and mean arterial pressure. Interestingly, MDL28170 and swimming exercise preconditioning improved heart function and arterial pressure in the ischemia/reperfusion rats. Ischemia/reperfusion increased the proteolysis of α-fodrin, a substrate of calpain, and the membrane recruitment of calpain1, a catalytic subunit of calpain. Furthermore, ischemia/reperfusion damaged cardiomyocyte membrane, as reflected by increases in intracellular accumulation of Evans blue and loss of dystrophin. Of note, all these phenomena were blocked by MDL28170 and swimming exercise preconditioning. Conclusion Exercise preconditioning protects cardiomyocyte membrane from ischemia/reperfusion injury, and the inhibition of calpain activity is involved in this process.