姜黄素复合有氧运动对非酒精性脂肪肝大鼠肝功能的改善作用

摘要/Abstract

摘要： 目的：研究姜黄素与有氧运动相结合对非酒精性脂肪肝（non-alcoholic fatty liver disease，NAFLD）大鼠肝功能改善的效果及机制。方法：雄性SD大鼠随机分为安静对照组、NAFLD模型组、有氧运动干预组、姜黄素干预组和姜黄素复合有氧运动干预组，每组8只。全自动生化仪检测大鼠血清谷丙转氨酶（alanine aminotransferase，ALT）、谷草转氨酶（aspartate aminotransferase，AST）活性及总胆固醇（total cholesterol，TC）、总甘油三酯（total triglyceride，TG）、低密度脂蛋白胆固醇（low-density lipoprotein cholesterol，LDL-C）、高密度脂蛋白胆固醇（high-density lipoprotein cholesterol，HDL-C）水平；通过苏木素-伊红、油红O和电子染色法观察大鼠肝组织形态、脂质沉积及超微结构变化；采用实时荧光定量聚合酶链式反应、免疫组化和蛋白质印迹法检测大鼠肝腺苷酸活化蛋白激酶（adenosine monophosphate-activated protein kinase，AMPK）、磷酸化腺苷酸活化蛋白激酶（phosphorylated adenosine monophosphate-activated protein kinase，p-AMPK）、哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）、卷曲螺旋肌球蛋白样B细胞淋巴瘤-2相互作用蛋白-1（coiled-coil myosin-like B-cell lymphoma-2-interacting protein-1，Beclin-1）、选择性自噬接头蛋白-1（sequestosome-1，SQSTM1/P62）、微管相关蛋白1轻链3-Ⅰ（microtubule-associated protein 1 light chain 3-Ⅰ，LC3-Ⅰ）、微管相关蛋白1轻链3-Ⅱ（microtubule-associated protein 1 light chain 3-II，LC3-Ⅱ）mRNA和蛋白质表达水平。结果：8周高脂饮食成功诱导大鼠出现NAFLD。姜黄素和/或有氧运动干预可改善NAFLD大鼠肝超微结构损伤、病理变化及脂质沉积；显著降低血清TC、TG、LDL-C水平及AST和ALT活性；上调Beclin-1、LC3-II mRNA表达水平以及p-AMPK、Beclin-1、LC3-II蛋白质表达水平和p-AMPK/AMPK、LC3-II/LC3-Ⅰ蛋白质表达水平比值，下调mTOR、P62 mRNA和蛋白质表达水平，提升细胞自噬水平。姜黄素与有氧运动在血清TC、TG水平和ALT、AST活性及肝mTOR、Beclin-1、P62 mRNA表达水平和p-AMPK、P62、LC3-Ⅱ蛋白质表达及LC3-Ⅱ/LC3-Ⅰ蛋白质表达比值上存在交互效应。结论：姜黄素和/或有氧运动干预通过调控AMPK/mTOR信号通路，适度增强细胞自噬水平，改善NAFLD大鼠肝脏结构和功能。其中，姜黄素复合有氧运动干预效果最佳。

关键词: 姜黄素, 有氧运动, 腺苷酸活化蛋白激酶/哺乳动物雷帕霉素靶蛋白信号通路, 自噬, 非酒精性脂肪肝

Abstract: Objective: To explore the improvements and mechanisms of curcumin combined with aerobic exercise on liver function in rats with non-alcoholic fatty liver disease (NAFLD). Methods: Male SD rats were randomly divided into control group, NAFLD model group, aerobic exercise intervention group, curcumin intervention group and curcumin combined with aerobic exercise intervention group, 8 in each group. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), total triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) were detected by automatic biochemistry analyzer; histomorphology, hepatic lipid deposition and ultrastructural changes were detected by hematoxylin-eosin, Oil Red O and electronic staining; hepatic adenosine monophosphate-activated protein kinase (AMPK), phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), mammalian target of rapamycin (mTOR), coiled-coil myosin-like B-cell lymphoma-2-interacting protein-1 (Beclin-1), sequestosome-1 protein (SQSTM1/P62), microtubule-associated protein 1 light chain 3-Ⅰ (LC3-Ⅰ) and microtubule-associated protein 1 light chain 3-Ⅱ (LC3-Ⅱ) mRNA and protein expression were detected by quantitative real-time polymerase chain reaction, immunohistochemistry and western blot. Results: Eight-week high-fat diet induced NAFLD in rats successfully. Curcumin and/or aerobic exercise intervention could decrease serum TC, TG, LDL-C significantly, improve abnormality of liver lipid deposition; decrease serum AST and ALT, improve pathologic changes in liver; up-regulate hepatic Beclin1, LC3-II mRNA expression and p-AMPK, Beclin1, LC3-II protein expression, p-AMPK/AMPK and LC3-II/LC3-Ⅰ ratio of protein, down-regulate mTOR, P62 mRNA and protein expression, alleviate ultrastructural damage, enhance cellular autophagy. Curcumin and aerobic exercise had interactive effects on serum TC and TG levels, ALT and AST activity, hepatic mTOR, Beclin-1, P62 mRNA expression, p-AMPK, P62, LC3-Ⅱ protein expression and LC3-II/LC3-Ⅰ ratio of protein. Conclusion: Curcumin and/or aerobic exercise intervention can improve liver structure and function in NAFLD rats by modulating AMPK/mTOR signaling pathway and enhancing cellular autophagy moderately. Thereinto, Curcumin combined with aerobic exercise intervention is the most effective.

Key words: curcumin, aerobic exercise, adenosine monophosphate-activated protein kinase/ mammalian target of rapamycin signaling pathway, autophagy, nonalcoholic fatty liver

中图分类号:

TS218
G804.7

胡戈秦菲曹建民吉喆周绮云周海涛. 姜黄素复合有氧运动对非酒精性脂肪肝大鼠肝功能的改善作用[J]. 食品科学.

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