Effects and Mechanism of Chaperone-Mediated Autophagy on Severe Acute Pancreatitis-Associated Liver Injury
10.11969/j.issn.1673-548X.2025.04.009
- VernacularTitle:分子伴侣介导的自噬在重症急性胰腺炎相关肝损伤中的作用及其机制
- Author:
Zhongbiao LI
1
;
Min DU
;
Jiang WANG
Author Information
1. 266071 青岛大学青岛医学院
- Publication Type:Journal Article
- Keywords:
CMA;
Oxidative stress;
Nrf2;
Acute liver injury;
Severe acute pancreatitis
- From:
Journal of Medical Research
2025;54(4):39-44
- CountryChina
- Language:Chinese
-
Abstract:
Objective Acute liver injury(ALI)exacerbates the condition of patients with severe acute pancreatitis(SAP)and neg-atively affects their prognosis.Recent studies have highlighted the crucial role of chaperone-mediated autophagy(CMA)in regulating liver injury.This study aims to explore the effects of CMA on the pathophysiologic mechanisms of SAP-induced acute liver injury(SAP-ALI).Methods A SAP rat model was established via retrograde injection of 5％sodium taurocholate into the biliary-pancreat-ic duct.Rats were randomly divided into the sham operation(Sham)group,SAP group,CMA activator(AR7)control group,and AR7+SAP treatment group.After 24hours,serum amylase(AMY),liver function,and oxidative stress-specific markers were meas-ured.HE staining was used to evaluate the pathological injury in the pancreatic and liver tissues.The expression levels of lysosomal-as-sociated membrane protein 2 A(LAMP2A),GAPDH,keleh-like ECH-associated protein 1(Keap1),and nuclear factor E2-related factor 2(Nrf2)proteins and LAMP2A,Nrf2mRNA were analyzed by Western blot,immunofluorescence staining,and qRT-PCR.Results AR7 pretreatment significantly improved liver function(P＜0.05),alleviated the pathological damage to the pancreas and liver and enhanced the antioxidant stress capacity(P＜0.05)of SAP-ALI rats.The downregulation of LAMP2A(P＜0.05)and accumula-tion of the CMA substrate GAPDH(P＜0.05)indicated CMA dysfunction in SAP-ALI.Furthermore,AR7-induced upregulation of CMA promoted the activation of the Keap1/Nrf2 pathway in liver(P＜0.05),contributing to its antioxidative effect.Conclusion Our study demonstrates that CMA dysfunction is involved in the pathological process of SAP-induced acute liver injury.AR7-induced CMA reactivation regulates the Keap1/Nrf2 antioxidant pathway,providing protection against SAP-induced acute liver injury in rats.
