肝纤维化（liver fibrosis， LF）是多种慢性肝病的共同病理阶段，可逐步发展为肝硬化甚至肝癌，目前临床上仍缺乏有效的治疗药物。肝星状细胞（hepatic stellate cells， HSCs）是LF的核心效应细胞，HSCs活化后会分泌大量细胞外基质在肝内沉积，最终驱动LF发展。因此靶向HSCs的治疗成为逆转LF的关键，其中抑制HSCs活化、促进活化HSCs程序性死亡是较为成熟的传统方向，而近年来，诱导活化态HSCs失活已成为新颖且具前景的研究热点。本文将简要回顾前2种传统策略的研究现状，重点阐述诱导活化态HSCs失活的分子机制，并系统总结天然产物在上述3种调控方式中的作用机制与研究进展，以期为深入阐明LF发病机制、挖掘天然产物治疗LF的潜在靶点提供新视角。

Liver fibrosis （LF）， a common pathological stage observed in various chronic liver diseases， can progress to cirrhosis and even hepatocellular carcinoma. Currently， effective clinical therapeutic agents for LF remain limited. Hepatic stellate cells （HSCs） are recognized as the primary effector cells in LF. When activated， HSCs secrete large amounts of extracellular matrix， resulting in excessive deposition within the liver and ultimately contributing to the progression of LF. Therefore， targeting HSCs is crucial for reversing LF. While traditional approaches focus on inhibiting HSCs activation and promoting programmed cell death of activated HSCs， inducing the quiescence of activated HSCs has emerged as a novel and promising research area in recent years. This article briefly reviews the current status of the first two traditional strategies， elucidates the molecular mechanisms involved in the inactivation of activated HSCs， and systematically summarizes the mechanisms of action and research progress of natural products in these three regulatory approaches. The aim is to provide new perspectives for enhancing the understanding of LF pathogenesis and identifying potential therapeutic targets of natural products for LF treatment.

R575.2

国家自然科学基金（82360917）