HMGB1-RAGE信号轴在肝脏缺血再灌注损伤中作用的研究进展

Research progress in the role of HMGB1-RAGE signaling axis in hepatic ischemia-reperfusion injury

肝脏缺血再灌注损伤(HIRI)是缺血损伤后再灌注所致的一种肝损伤,临床表现为肝恢复血供后出现肝功能损伤、黄疸甚至多器官功能衰竭等一系列恶化现象,严重影响患者转归及预后。及时再灌注处理和降低再灌注损伤是临床预防和治疗HIRI的关键。HIRI的本质是一种无菌炎症反应。高迁移率组蛋白1(HMGB1)是HIRI的一种重要中间介质,是多种细胞类型效应器,参与HIRI的发生。HMGB1的糖基化终末产物受体(RAGE)信号轴在HIRI中发挥关键作用,但其机制尚不明确。归纳总结了近年来与HMGB1-RAGE信号轴在HIRI中促炎机制相关的研究,探讨了HMGB1-RAGE信号通路与HIRI的关系,并以HMGB1-RAGE信号轴为靶点,总结了通过手术操作、缺血预处理、药物和基因治疗等方法预防和治疗HIRI的研究进展。

Hepatic ischemia-reperfusion injury(HIRI)is a kind of liver injury caused by reperfusion after ischemic injury,which is clinically manifested by a series of deterioration phenomena such as liver function impairment,jaundice and even multi-organ failure after restoration of blood supply to the liver.HIRI seriously affects the patient's regression and prognosis.The essence of HIRI is a sterile inflammatory response.High mobility histone 1(HMGB1)is an important intermediate mediator of HIRI and is a multiple cell type effector involved in HIRI.The receptor for glycosylated end products(RAGE)signaling axis of HMGB1 plays a key role in HIRI,but its mechanism is unclear.In this paper,the recent studies related to the pro-inflammatory mechanism of HMGB1-RAGE signaling axis in HIRI were summarized,and the relationship between HMGB1-RAGE signaling pathway and HIRI was discussed.The research progress of preventing and treating HIRI with surgical operation,ischemic preconditioning,drug and gene therapy using HMGB1-RAGE signaling axis as the target was reviewed.