坏死性凋亡在肝纤维化中的作用
DOI: 10.12449/JCH240827
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摘要: 肝纤维化作为各种慢性肝病向肝硬化发展的关键环节,影响其预后与转归。坏死性凋亡是一种新型的程序性细胞死亡模式,已被证明在多种疾病的病理生理中发挥重要作用,同样也被认为是改善肝纤维化的潜在靶点。不同类型的肝内细胞(包括肝细胞、肝星状细胞、肝巨噬细胞及肝窦内皮细胞)发生坏死性凋亡,可对肝纤维化发挥促进或抑制作用,本文着重阐述上述作用机制,并讨论靶向坏死性凋亡介导的肝纤维化的治疗策略。Abstract: As a crucial link in the progression of various chronic liver diseases to liver cirrhosis, liver fibrosis affects the prognosis and outcome of chronic liver diseases. Necrotosis is a novel pattern of programmed cell death (PCD), and studies have shown that it plays an important role in the pathophysiology of various diseases and is considered a potential target for improving liver fibrosis. Necroptosis of various types of intrahepatic cells (including hepatocytes, hepatic stellate cells, liver macrophages, and hepatic sinusoidal endothelial cells) can promote or inhibit liver fibrosis. This article elaborates on the above mechanisms and discusses the therapeutic strategies for targeting liver fibrosis mediated by necroptosis.
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Key words:
- Hepatic Fibrosis /
- Necroptosis /
- Hepatic Stellate Cells
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表 1 肝内细胞坏死性凋亡与肝纤维化的关系
Table 1. Relationship between intrahepatic cell necroptosis and liver fibrosis
肝内细胞类型 发生坏死性凋亡后
对肝纤维化的影响
主要作用机制 治疗思路 肝细胞 促进 促进促炎因子DAMP释放,诱导HSC活化 抑制其坏死性凋亡 HSC 抑制 直接抑制HSC活化 靶向促进其发生坏死性凋亡 M1巨噬细胞 抑制 促进促炎因子DAMP释放,诱导HSC活化 靶向促进其发生坏死性凋亡 M2巨噬细胞 促进 吞噬死亡肝细胞,清除促炎因子,抑制HSC活化 抑制其坏死性凋亡 肝窦内皮细胞 促进 调节肝脏内环境能力受损,促进HSC活化 抑制其坏死性凋亡 -
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