摘要
肝窦阻塞综合征(HSOS)是一类主要与摄入吡咯生物碱及造血干细胞移植治疗后有关的肝脏继发性血管性疾病,可导致严重的肝功能障碍甚至多器官功能衰竭而死亡.HSOS主要病理表现为肝窦扩张阻塞、肝细胞凝固性坏死及肝小叶炎症,而肝窦内皮细胞(LSECs)损伤是HSOS病理发生进程中的关键启动事件.目前认为多种病因和机制参与LSECs的损伤,并继发凝血纤溶失调、氧化应激和炎症反应从而导致HSOS发生,但其机制尚未完全阐明.近年来,免疫炎性机制在LSECs损伤中的作用越来越受到重视.现就HSOS的流行病学、病因学和病理改变进行概述,回顾了 LSECs的生理功能、LSECs损伤的常见病因机制和LSECs损伤在HSOS发病中的关键作用,尤其聚焦近年来免疫炎性机制在LSECs损伤中的作用和研究进展.深入研究并阐明免疫炎性机制在LSECs损伤和HSOS发病中的作用,将为筛选鉴定HSOS诊断的新标志物和药物治疗靶点提供可行的研发思路.
Abstract
Hepatic sinusoidal obstruction syndrome(HSOS)is a type of secondary vascular disease of the liver that is mainly associated with the ingestion of pyrrole alkaloids(PAs)and hematopoietic stem cell transplantation(HSCT)treatment,resulting in severe liver dysfunction,multiple organ failure,and even death.Hepatic sinusoidal dilatation and obstruction,hepatocyte coagulative necrosis,and hepatic lobular inflammation are the main pathological manifestations of HSOS.The key initiating process for the pathogenesis of HSOS is damage to liver sinusoidal endothelial cells(LSECs).Currently,it is believed that LSECs are damaged by the involvement of multiple etiologies and mechanisms,and secondary coagulation and fibrinolysis disorders,oxidative stress,and inflammatory responses are the occurrence contributors to HSOS;however,the mechanism has not been fully elucidated.Therefore,the role of immune-inflammatory mechanisms has received increasing attention in LSEC damage.This article provides an overview of the epidemiology,etiology,and pathological changes of HSOS and reviews the physiological functions,common etiological damage mechanisms,and the key role of LSEC damage in the pathogenesis of HSOS,with a special focus on the role and research progress of immune-inflammatory mechanisms for LSEC damage in recent years.Furthermore,we believe that in-depth study and elucidation of the role of immune-inflammatory mechanisms in LSEC damage and the pathogenesis of HSOS and diagnosis will provide feasible research and development ideas for the screening and identification of new markers and drug treatment targets for HSOS.
基金项目
山东省自然科学基金面上项目(ZR2021MH324)
山东省自然科学基金青年基金(ZR2020QH032)
维普
万方数据