畜牧与饲料科学 ›› 2023, Vol. 44 ›› Issue (4): 29-40.doi: 10.12160/j.issn.1672-5190.2023.04.005

• 基础研究 • 上一篇    下一篇

非酒精性脂肪性肝病发展及向肝癌转变过程中的分子调控机理研究进展

卞康坤,包玉龙,王利   

  1. 内蒙古医科大学基础医学院,内蒙古 呼和浩特 010110
  • 收稿日期:2023-05-19 出版日期:2023-07-30 发布日期:2023-08-30
  • 通讯作者: 王利(1981—),男,副教授,博士,硕士生导师,主要从事肿瘤免疫与肝损伤再生研究工作。
  • 作者简介:卞康坤(1996—),男,硕士研究生,主要研究方向为蒙药治疗肝损伤疾病。
  • 基金资助:
    内蒙古自治区科技计划项目(2021GG0098)

Research Progress in Molecular Regulatory Mechanisms in the Development of Non-alcoholic Fatty Liver Disease and Its Transition to Liver Cancer

BIAN Kangkun,BAO Yulong,WANG Li   

  1. College of Basic Medicine,Inner Mongolia Medical University,Hohhot 010110,China
  • Received:2023-05-19 Online:2023-07-30 Published:2023-08-30

摘要:

炎症和纤维化是非酒精性脂肪性肝病(non-alcohol fatty liver disease,NAFLD)发展过程中的重要标志。在NAFLD的发展进程及向肝癌的转变过程中有多种信号通路发挥关键作用,调控肝细胞的进一步损伤及恶性转变。Hippo信号通路通过调节脂质代谢、肝星状细胞(hepatic stellate cells,HSC)激活等过程控制NAFLD进程;肝脏中PI3K/AKT信号通路的活化,可以抑制炎症因子的表达,增强肝脏抗炎能力并抑制肝脏中炎症因子的活性,从而缓解肝细胞损伤;TGF-β信号通路通过进一步促进慢性炎症状态下的肝细胞凋亡、HSC激活等加重非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH);AMPK信号通路在糖类及脂肪代谢调节、能量调控及向肝癌的转化过程方面发挥重要作用;NF-κB主要在促炎基因表达中起作用,抑制该通路可以减轻脂肪性肝炎和肝纤维化进程。综述NAFLD发展进程及向肝癌转变过程中涉及的主要信号通路的调控机理研究进展,以期尽可能在NAFLD的早期阶段阻止其进一步病变及向肝癌的转变,为临床NAFLD的靶向治疗提供参考。

关键词: 非酒精性脂肪性肝病, 非酒精性脂肪性肝炎, 肝纤维化, 肝癌, 调控机制, 信号通路

Abstract:

Inflammation and fibrosis are important signs in the development of non-alcoholic fatty liver disease (NAFLD). There are multiple signaling pathways that exert key roles in the progression of NAFLD and its transition to liver cancer, regulating further damage and malignant transition of hepatocytes. Among them, the Hippo signaling pathway controls the progression of NAFLD by regulating lipid metabolism and activating hepatic stellate cells (HSC); the activation of the PI3K/AKT signaling pathway can inhibit the expression of inflammatory factors, enhance anti-inflammatory capabilities, and reduce the activity of inflammatory factors in the liver, thereby alleviating the degree of hepatocyte damages; the TGF-β signaling pathway aggravates non-alcoholic steatohepatitis (NASH) by further promoting hepatocyte apoptosis and HSC activation under chronic inflammatory conditions; the AMPK signaling pathway plays important roles in carbohydrate and fat metabolism regulation, energy regulation and the transition from NAFLD to liver cancer; the NF-κB signaling pathway regulates the expression of pro-inflammatory genes, and the process of steatohepatitis and liver fibrosis can be reduced by inhibiting this pathway. This paper presents a review on the research progress in the regulatory mechanisms of the main signaling pathways involved in the development of NAFLD and its transition to liver cancer, in hoping to prevent further lesions and transition to liver cancer in the early stage of NAFLD as much as possible, and to provide references for targeted therapy of NAFLD in clinical practice.

Key words: non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, hepatic fibrosis, liver cancer, regulatory mechanism, signaling pathway

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