Molecular mechanisms and therapeutic strategies of endoplasmic reticulum stress-mediated hepatic ischemia-reperfusion injury
10.13406/j.cnki.cyxb.003823
- VernacularTitle:内质网应激介导的肝缺血再灌注损伤的分子机制与治疗策略
- Author:
Chang LIU
1
;
Rui TAO
;
Qihui HU
;
Jing LUO
;
Cong CHEN
Author Information
1. 重庆医科大学附属璧山医院肝胆外科,重庆 402760
- Keywords:
endoplasmic reticulum stress;
hepatic ischemia-reperfusion;
unfolded protein response;
apoptosis;
therapeutic target
- From:
Journal of Chongqing Medical University
2025;50(7):951-956
- CountryChina
- Language:Chinese
-
Abstract:
Hepatic ischemia-reperfusion injury(IRI)is a pathological phenomenon that commonly occurs during liver surgery and transplantation.It leads to serious tissue damage and affects liver function.The mechanisms behind IRI are complex,involving oxida-tive stress,inflammatory responses,and calcium homeostasis disorder.Recently,scientists have paid more attention to the role of endo-plasmic reticulum stress(ERS)in IRI.ERS activates three classical signaling pathways,PERK,IRE1,and ATF6,through the unfolded protein response(UPR),aiming to preliminarily restore endoplasmic reticulum homeostasis and protect cells.However,if the stress re-sponse is excessive or persistent,ERS can activate apoptosis signaling pathways,such as CHOP and Bax/Bak,worsening cell injury.Additionally,ERS is closely related to other cellular stress responses,such as autophagy and oxidative stress,which jointly affect the survival and death of hepatocytes.Regulation of ERS,especially interventions targeting the three UPR pathways,is considered as a po-tential therapeutic pathway for alleviating hepatic IRI.Pharmacological interventions,such as 4-phenylbutyric acid and taurocholic acid,and gene therapies,such as knocking out PERK or IRE1,have shown positive effects in protecting liver function while inhibiting ERS.This paper reviews the mechanism of action of ERS in hepatic IRI,focuses on the specific roles of the three UPR pathways and their potential as therapeutic targets,and explores the future of re-lated therapeutic strategies.
