Zhou Juntao, Wang Jianqiao, Zhang Lijuan, Zhang Chengliang, Tian Cheng
Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Pharmaceuticals (Basel). 2025 Jun 14;18(6):893. doi: 10.3390/ph18060893.
Liver fibrosis is a common pathological manifestation of various chronic liver diseases, distinguished by the excessive accumulation of the extracellular matrix. If unresolved, liver fibrosis can progress to cirrhosis or hepatocellular carcinoma. Fenestrae are important structures of liver sinusoidal endothelial cells (LSECs) regulating hepatic substance exchange, immune response and hemodynamics. The loss of this structure is usually accompanied by dysfunction of LSECs, which disrupts normal liver physiology by impairing hepatic substance exchange, compromising liver microcirculation, and activating hepatic stellate cells (HSCs). This cascade of events ultimately contributes to the onset and development of liver fibrosis. Oxidative stress, impairment of the NO signaling pathway, actin-myosin complex remodeling and pathological angiogenesis are considered to be the main mechanisms underlying LSEC defenestration. Recently, research on the treatment of LSEC defenestration has made notable progress, and findings suggest a potential value in the application of anti-fibrotic therapies. This article expounds the important correlation between defenestration of LSECs and liver fibrosis, while also reviews therapeutic agents and approaches targeting this pathological process.
肝纤维化是各种慢性肝病常见的病理表现，其特征为细胞外基质过度积聚。若不加以解决，肝纤维化可进展为肝硬化或肝细胞癌。窗孔是肝窦内皮细胞（LSECs）的重要结构，调节肝脏物质交换、免疫反应和血流动力学。这种结构的丧失通常伴随着LSECs功能障碍，通过损害肝脏物质交换、破坏肝脏微循环和激活肝星状细胞（HSCs）来扰乱正常肝脏生理功能。这一系列事件最终导致肝纤维化的发生和发展。氧化应激、NO信号通路受损、肌动蛋白-肌球蛋白复合物重塑和病理性血管生成被认为是LSEC窗孔丧失的主要机制。最近，关于LSEC窗孔丧失治疗的研究取得了显著进展，研究结果表明抗纤维化疗法具有潜在应用价值。本文阐述了LSECs窗孔丧失与肝纤维化之间的重要关联，同时还综述了针对这一病理过程的治疗药物和方法。
