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茶叶科学 ›› 2024, Vol. 44 ›› Issue (2): 329-340.doi: 10.13305/j.cnki.jts.2024.02.012

• 研究报告 • 上一篇    下一篇

黑茶水提物通过介导AMPK/mTOR信号通路调控自噬干预非酒精性脂肪肝的机制研究

李琳莉1, 夏旭婷1, 施敏1, 葛俊1, 毛彩薇1, 喻长红2,*, 刘富林1,*   

  1. 1.湖南中医药大学,湖南 长沙 410208;
    2.常德市第一中医医院,湖南 常德 415000
  • 收稿日期:2023-11-15 修回日期:2024-01-03 出版日期:2024-04-15 发布日期:2024-04-30
  • 通讯作者: * 13507480342@sina.cn;616217372@qq.com
  • 作者简介:李琳莉,女,硕士研究生,主要从事中医治则与治法研究。
  • 基金资助:
    湖南省自然科学基金面上项目(2022JJ30437)、湖南省中医药科研计划重点项目(C2022033)、湖南省教育厅重点项目(21A0232)、湖南省中医药科研项目(B2023151)、常德市科技教育厅重点项目(2021SK055)、湖南中医药大学研究生创新项目(2023CX173)

Mechanism of Dark Tea Water Extract in Regulating Autophagy in Non-Alcoholic Fatty Liver via the AMPK/mTOR Signaling Pathway

LI Linli1, XIA Xuting1, SHI Min1, GE Jun1, MAO Caiwei1, YU Changhong2,*, LIU Fulin1,*   

  1. 1. Hunan University of Traditional Chinese Medicine, Changsha 410208, China;
    2. The First Chinese Medicine Hospital of Changde, Changde 415000, China
  • Received:2023-11-15 Revised:2024-01-03 Online:2024-04-15 Published:2024-04-30

摘要: 为探讨安化黑茶水提物对高脂高糖(HFHS)饮食诱导的非酒精性脂肪肝病(NAFLD)小鼠调控自噬改善脂肪变性的作用机制,将雄性C57BL/6J小鼠分为正常组、模型组、西药组(10 mg·kg-1)、黑茶低剂量组(0.75 g·kg-1)、中剂量组(1.5 g·kg-1)、高剂量组(3.0 g·kg-1)。采用HFHS饮食诱导小鼠NAFLD模型,造模的同时灌胃给药10周;试验结束后检测小鼠的肝指数、血脂、肝功能、肝脏病理指标、自噬指标及自噬相关信号通路表达水平。结果表明,与正常组相比,模型组小鼠肝指数和总胆固醇(CHO)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、谷草转氨酶(AST)、谷丙转氨酶(ALT)含量显著升高,高密度脂蛋白胆固醇(HDL-C)含量明显降低;小鼠肝脏出现了脂肪变性的迹象,伴有大量大小不一的脂滴;微管相关蛋白1轻链3B(LC3B)、Bcl-2相互作用蛋白1(Beclin1)、磷酸化腺苷酸活化蛋白激酶/腺苷酸活化蛋白激酶(p-AMPK/AMPK)表达明显降低,隔离体蛋白1(p62)、磷酸化哺乳动物雷帕霉素靶蛋白/哺乳动物雷帕霉素靶蛋白(p-mTOR/mTOR)表达显著上升。与模型组相比,灌胃黑茶水提物可降低NAFLD小鼠肝指数和血清CHO、TG、LDL-C、AST、ALT水平,以及p62、p-mTOR/mTOR蛋白表达水平,升高血清HDL-C含量,以及LC3B、Beclin1、p-AMPK/AMPK蛋白表达水平;组织染色结果和透射电镜观察均表明肝脏的病理状态得到了改善。综上所述,黑茶水提物可能通过激活AMPK/mTOR信号通路调控自噬,减轻小鼠肝脏脂肪变性,从而改善NAFLD。

关键词: 非酒精性脂肪肝病, 黑茶, AMPK/mTOR, 自噬

Abstract: This study aimed to investigate the intricate mechanisms underlying the modulatory effects of Anhua dark tea on autophagy to ameliorate steatosis induced by a high-fat and high-sucrose diet (HFHS) in mice with non-alcoholic fatty liver disease (NAFLD). Male C57BL/6J mice were divided into different groups, including a normal group, a model group, a Western medicine group (10 mg·kg-1), and various doses of dark tea groups (0.75, 1.5, 3.0 g·kg-1). The therapeutic regimen was administered concurrently with the modeling process for a duration of 10 weeks using the HFHS-induced NAFLD model. At the end of the experiment, liver indices, blood lipids, liver function, liver pathology indicators, autophagy markers, and expression levels of key genes in the autophagy-related signaling pathway were assessed. Comparative analyses with the normal group revealed significant increases in liver index and levels of serum cholesterol (CHO), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), as well as a substantial reduction in high-density lipoprotein cholesterol (HDL-C) levels in the model group. The liver of the mice exhibits signs of steatosis, characterized by an abundance of lipid droplets of different sizes. Protein expression analysis reveals a marked decrease in the levels of microtubule-associated protein light-chain-3B (LC3B), Bcl-2-interacting coiled-coil protein 1 (Beclin1), and phosphorylated adenosine monophosphate-activated protein kinase/adenosine monophosphate-activated protein kinase (p-AMPK/AMPK). Conversely, there was a significant increase in the levels of sequestosome-1 (p62) and phosphorylated mammalian target of rapamycin/mammalian target of rapamycin (p-mTOR/mTOR). Compared to the model group, gavage with dark tea decreased the liver index, serum levels of CHO, TG, LDL-C, AST, ALT, p62, and p-mTOR/mTOR in NAFLD mice, and increased serum HDL-C, along with LC3B, Beclin1, and p-AMPK/AMPK protein levels. The improvements were confirmed by tissue staining results and observations using transmission electron microscopy. In summary, our findings suggest that dark tea, by activating the AMPK/mTOR signaling pathway, may regulate autophagy, thereby alleviating hepatic steatosis and improving non-alcoholic fatty liver disease (NAFLD).

Key words: nonalcoholic fatty liver disease, dark tea, AMPK/mTOR, autophagy

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