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

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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(n 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(n 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(n 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(n 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(n P<0.01)。n 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.
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