基于SIRT1轴的线粒体增殖和自噬通路探讨有氧运动对NASH大鼠脂肪性肝炎的影响

Effect of Aerobic Exercise on NASH in Rats Based on SIRT1 Axis Mitochondrial Proliferation and Autophagy Pathway

目的:研究有氧运动抑制高脂饮食导致的肝脂肪变性、炎症和纤维化的效果,探讨有氧运动促进肝细胞线粒体增殖和线粒体自噬、改善脂肪肝细胞线粒体质量控制、抑制氧化应激的可能机制。方法:雄性健康SD大鼠随机分为普通安静组(ND)、高脂安静组(C)和高脂长期运动组(RE),分别给予普通饲料或高脂饲料,高脂组前7周给予普通饲料,后16周给予高脂饲料。RE组大鼠进行跑台运动,25 m/min,60min/d,5 d/周,23周。结果:C组大鼠发生脂肪性肝炎和肝纤维化,NAS评分、血脂、血ALT和肝MDA较ND组显著性升高,肝SOD活性较ND组显著性下降;RE组大鼠NAS评分、血脂、ALT水平和肝MDA含量较C组显著性下降,肝SOD活性显著性升高;肝细胞线粒体增殖和自噬调控相关的转录因子SIRT1、Parkin和LC3 II的表达上,RE组较C组显著性升高;RE组肝细胞COX IV表达和线粒体膜电位较C组显著性增加。结论:有氧运动抑制NAFLD大鼠肝炎和肝纤维化的发生,其机制与促进SIRT1表达,改善线粒体自噬和增殖功能和减少ROS生成、抑制氧化应激有关。

The purposes of this study were to investigate the effect of regular aerobic exercise on the liver steatosis,inflammation and fibrosis reduced by high fat diet,and to detect the mechanisms of exercise improving mitochondrial proliferation and autophagy and quality,inhibiting oxidative stress. Methods： Male SD rats were randomly divided into normal diet and sedentary group（ ND）,high fat diet and sedentary group（ C）,and high fat diet and regular aerobic exercise group（ RE）. Rats of C and RE groups were given normal diet for the early seven weeks,and then given high fat diet in the rest time. Rats of RE group underwent treadmill running at 25 m / min,60 min /d,5d / w,and 23 weeks in total. Results： There were steatohepatitis and fibrosis of rats in C group. Compared with C group,the NAS,serum lipid,ALT,MDA in ND and RE groups were lower,but SOD was higher. Compared with C group,the expressions of SIRT1,Parkin,LC3 II,COX IV,and the hepatocyte mitochondrial membrane potential were significantly higher. Conclusion： Regular aerobic exercise could inhibit the occurrence of steatohepatitis and fibrosis of NAFLD rats,the mechanism is about exercise improving SIRT1 expression,promoting mitochondrial proliferation and autophagy,inhibiting oxidative stress,decreasing ROD expression.