受体相互作用蛋白激酶调控非酒精性脂肪肝中细胞程序性坏死的研究进展

doi:10.16098/j.issn.0529-1356.2020.04.025

摘要/Abstract

摘要：

非酒精性脂肪性肝病（NAFLD）是一种常见的慢性肝病，如果得不到有效控制，则会进一步发展为非酒精性脂肪性肝炎（NASH），进而引起肝纤维化、肝硬化，甚至癌变。程序性坏死是近年来发现的一种新型细胞程序性死亡方式，由受体相互作用蛋白激酶（RIPK）介导所致，最终可以导致细胞膜溶解破裂，引发炎症。RIPK家族作为细胞内和细胞外应激的重要传感器，诱导调控程序性坏死的发生，并参与炎症及其他免疫反应。近年来研究表明，RIPK调控的程序性坏死在非酒精性脂肪性肝病的发生发展中具有重要作用，在动物NAFLD/NASH模型中，RIPK的表达情况与肝脂肪变性程度密切相关。在一些临床研究中亦观察到，NAFLD/NASH患者比健康人RIPK表达水平上升。但程序性坏死到底是加速肝病进程的因素，还是肝病发展过程中的保护因素，仍然没有定论。有研究表明，RIPK抑制剂可能为NAFLD治疗提供方向。我们综述了程序性坏死的分子机制及与非酒精性脂肪性肝病的关系，以及RIPK在其中扮演的重要角色，并总结了其在NAFLD/NASH治疗方面的研究进展，为进一步探究其机制，探索新的治疗手段提供理论依据。

关键词: 非酒精性脂肪肝病, 非酒精性脂肪性肝炎, 程序性坏死, 受体相互作用蛋白激酶

Abstract:

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, which might develop into nonalcoholic steatohepatitis (NASH), liver cirrhosis and even carcinoma without effective management. Necroptosis mediated by receptor interacting protein kinase (RIPK) is a novel type of programmed cell death discovered in recent years, which can eventually lead to cell membrane lysis and inflammation. As an important sensor of intracellular and extracellular stress, the RIPK family induces and regulates the activation of necroptosis, and is involved in inflammation and other immune responses. In recent years, studies have shown that RIPK-regulated necroptosis plays an important role in the development of NAFLD. In animal NAFLD/NASH model, the expression of RIPK is related to the degree of hepatic steatosis. In some clinical studies, it was also observed that RIPK expression levels were elevated in NAFLD/NASH patients compared with healthy controls. However, whether necroptosis is a factor which a celerates the progression of liver disease, or a protective factor in the development of liver disease, is still inconclusive. Some studies have shown that RIPK inhibitors may provide guidance for NAFLD treatment. This review provides the molecular mechanisms of necroptosis and its relationship with NAFLD, introduces the important role of RIPK, and summarizes its research progress in the treatment of NAFLD, providing a theoretical basis for further exploration of its mechanism and new treatments for NAFLD.

Key words: Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis, Necroptosis, Receptor interacting protein kinase

中图分类号:

Q291

郭翼宁范祺张卫光. 受体相互作用蛋白激酶调控非酒精性脂肪肝中细胞程序性坏死的研究进展 [J]. 解剖学报, 2020, 51(4): 626-630.

GUO Yi-ning FAN Qi ZHANG Wei-guang. Research progress on receptor interacting protein kinase regulated necroptosis in nonalcoholic fatty liver disease[J]. Acta Anatomica Sinica, 2020, 51(4): 626-630.

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