有氧运动对非酒精性脂肪肝大鼠肝组织雷帕霉素靶蛋白、核糖体蛋白S6激酶1和固醇调节元件结合蛋白1c表达的影响

Aerobic exercise inhibits mTOR,S6K1 and SREBP-1c signaling in non-alcoholic fatty liver disease

目的观察有氧运动对非酒精性脂肪肝大鼠肝组织雷帕霉素靶蛋白(mTOR)、核糖体蛋白S6激酶1(S6K1)、固醇调节元件结合蛋白1c(SREBP-1c)表达的影响。方法选取健康雄性SD大鼠30只,按随机数字表法分为正常组、模型组和运动组。正常组喂食基础饲料,模型组和运动组均喂食高脂饲料,运动组大鼠进行12周跑台训练。3组大鼠均于实验12周后取材,肝脏称重,并进行肝组织苏木精-伊红(HE)染色观察和肝组织炎症活动度评分,同时测定血清总胆固醇(TC)、甘油三酯(TG)、游离脂肪酸(FFA)、谷草转氨酶(AST)和谷丙转苷酶(ALT)含量的变化,采用免疫印迹方法检测肝组织mTOR、S6K1、SREBP-1c蛋白的表达。结果正常组大鼠肝脏组织形态学基本正常,肝索排列整齐,肝小叶结构完整清晰,未见脂肪变性及炎症细胞浸润;模型组大鼠可见弥漫性肝细胞脂肪变性,肝索紊乱,炎性细胞浸润;运动组大鼠肝索排列较模型组整齐,肝细胞脂滴明显减少,炎症细胞浸润减轻。运动组大鼠肝组织炎症活动度评分显著低于模型组(P<0.01);模型组大鼠血清TC、TG、FFA、ALT、AST水平均显著高于正常组(P<0.01);运动组大鼠血清TC、TG、FFA、ALT、AST水平均显著低于模型组(P<0.01)。模型组大鼠肝组织mTOR、S6K1、SREBP-1c的蛋白表达分别(1.12±0.24)、(1.34±0.35)、(0.84±0.12),均显著高于正常组(P<0.01);运动组大鼠肝组织mTOR、S6K1、SREBP-1c的蛋白表达分别为(0.54±0.18)、(0.61±0.21)、(0.41±0.15),均显著低于模型组(P<0.01)。结论有氧运动可以发挥防治非酒精性脂肪肝的作用,其机制可能与mTOR/S6K1/SREBP-1c信号通路的抑制相关。

Objective To observe the effect of aerobic exercise on the expression of the mechanistic target of rapamycin(mTOR),S6 protein kinase 1(S6K1)and sterol regulatory element binding protein 1c(SREBP-1c)in the liver tissues of rats modeling non-alcoholic fatty liver.Methods Thirty healthy male Sprague-Dawley rats were randomly assigned to a normal group(N),a control group(C)or an exercise group(E).The normal group was given basic feed,while the other two groups were on a high fat diet.Group E underwent a 12-week program of treadmill running,while the other two did no special exercise.The rats′livers were then resected and weighed.Hematoxylin-eosin staining(HE)staining was applied to get a hepatic inflammation activity score.Serum total cholesterol(TG),triglyceride(TC),free fatty acid(FFA),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected,and the expressions of mTOR,S6K1 and SREBP-1c in the liver tissue were determined using western blotting.Results In group N the histomorphology of the livers was basically normal,with the hepatic cords neatly arranged and the hepatic lobules intact with clear structure.No macrovesicular steatosis or inflamed cell infiltration was observed.In group C there was diffuse fatty degeneration with disordered hepatic cords and inflamed cell infiltration.In group E the hepatic cords were in good order,with lipid droplets and inflamed cell infiltration significantly less than in group N.The average hepatic inflammation activity score of group E was significantly lower than group C′s average,while the average TC,TG,FFA,ALT and AST levels of group C were significantly higher than those of groups N and E.The average expression of mTOR,S6K1 and SREBP-1c in group C were also significantly higher.Conclusion Aerobic exercise can help prevent and treat non-alcoholic fatty liver disease,at least in rats.Its mechanism may be related to the inhibition of the mTOR,S6K1 and SREBP-1c signaling pathways.