肝窦内皮细胞：慢性肝病进展的“帮凶”?

Liver sinusoidal endothelial cells: “accomplice” in chronic liver disease progression?

摘要

肝窦内皮细胞（liver sinusoidal endothelial cell，LSEC）是肝脏特异性的内皮细胞。生理条件下，LSEC具有开放的窗孔结构，可以完成肝细胞与血液之间小分子物质的高效交换，维持肝脏的滤过和代谢平衡，抑制肝星状细胞（hepatic stellate cell，HSC）活化，调节肝脏的免疫应答与耐受，构成了肝脏微循环的主要屏障。而在肝损伤过程中，LSEC发生毛细血管化，细胞衰老和内皮间质转化等表型改变，导致肝内血流阻力增加，物质交换障碍，促血管生成因子和炎性因子分泌增加，如不及时干预将会进一步加重肝损伤。因此，靶向干预LSEC功能障碍已成为慢性肝病治疗的新方向。文章系统阐述了LSEC在生理稳态和慢性肝病中的动态变化及具体作用机制，总结了目前靶向LSEC治疗慢性肝病的最新策略，同时也指出了当前研究的局限性及未来研究方向。

Abstract

Liver sinusoidal endothelial cells（LSEC）are liver-specific endothelial cells. Under physiological conditions，LSECs exhibit open fenestrae，facilitating the efficient bidirectional exchange of small molecules between hepatocytes and blood. They are crucial for maintaining hepatic filtration and metabolic homeostasis，suppressing the activation of hepatic stellate cells（HSC），and modulating hepatic immune responses and tolerance，thereby forming the principal barrier of the liver microcirculation. During liver injury，however，LSECs undergo phenotypic changes—including capillarization，cellular senescence，and endothelial-to-mesenchymal transition. These changes result in increased intrahepatic vascular resistance，impaired transvascular exchange，and enhanced secretion of pro-angiogenic and pro-inflammatory factors. In the absence of timely intervention，this pathological cascade can exacerbate liver damage. Therefore，therapeutic targeting of LSEC dysfunction has emerged as a novel strategy for chronic liver disease. This article systematically elaborates on the dynamic changes and specific mechanistic roles of LSECs in both physiological homeostasis and chronic liver disease，summarizes current therapeutic strategies aimed at LSECs，and also discusses existing research limitations and suggests future directions.

关键词

肝窦内皮细胞 / 慢性肝病 / 肝星状细胞

Key words

liver sinusoidal endothelial cell / chronic liver disease / hepatic stellate cell

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基金资助

国家自然科学基金(82400712)

江苏省基础研究计划自然科学基金青年基金(BK20230588)

江苏省高等学校基础科学（自然科学）研究面上项目(23KJB310031)

扬州市自然科学基金(YZ2023165)