南方医科大学学报2025，Vol.45Issue(9)：2026-2033,8.DOI:10.12122/j.issn.1673-4254.2025.09.22
低氧环境下NLRP3信号通路促进非酒精性脂肪性肝炎小鼠的肝细胞焦亡
NLRP3 signaling pathway promotes hepatocyte pyroptosis in mice with nonalcoholic steatohepatitis in hypoxic environment
摘要
Abstract
Objective To investigate the regulatory role of the NLRP3 signaling pathway in hepatocyte pyroptosis in nonalcoholic steatohepatitis(NASH)under hypoxia.Methods Twenty-four male C57BL/6 mice were randomized equally into hypoxic control(A),hypoxic NASH model(B),hypoxic NASH+NLRP3 inhibitor(C),and hypoxic NASH+caspase-1 inhibitor(D)groups.In groups B-D,the mice were fed a methionine choline-deficient(MCD)diet under hypoxic conditions(to simulate a 5000 m altitude)for 6 weeks;the mice in groups C and D received intraperitoneal injections of the respective inhibitors every other day.Results Compared with those in group A,the mice in group B showed significantly elevated serum levels of FBG,TC,TG,ALT and AST,increased liver lipid content,inflammatory cell infiltration and collagen fiber deposition,and enhanced hepatic expressions of NLRP3,caspase-1,IL-1β and GSDMD proteins,with obvious swelling,cristae breakage,vacuolization,and outer membrane disruption of the mitochondria,ribosome loss in the cytoplasm,destruction of the nuclear membrane,and pathological changes of the rough endoplasmic reticulum.Treatment with NLRP3 inhibitor and caspase-1 inhibitor both significantly lowered serum levels of TC,TG,ALT and AST(but without significantly affecting FBG)in the mouse models,and reduced liver lipid content,inflammatory cell infiltration,collagen deposition,and expression levels of NLRP3,caspase-1,GSDMD and IL-1β.The treatments also significantly improved pathological changes in the mitochondria,ribosomes and endoplasmic reticulum in liver tissues of the mice.Conclusion NLRP3 signaling pathway plays a key role in promoting hepatocyte pyroptosis in NASH mice under hypoxic condition,and inhibiting this pathway can effectively reduce liver inflammation,suggesting its potential as a therapeutic target for NASH treatment.关键词
低氧/非酒精性脂肪性肝炎/肝细胞焦亡/NLRP3炎症通路Key words
hypoxia/nonalcoholic steatohepatitis/hepatocyte pyroptosis/NLRP3 inflammatory pathway引用本文复制引用
罗善玉,朱强,闫玉翡,纪宗红,邹华杰,张瑞霞,巴应贵..低氧环境下NLRP3信号通路促进非酒精性脂肪性肝炎小鼠的肝细胞焦亡[J].南方医科大学学报,2025,45(9):2026-2033,8.基金项目
青海省科技计划项目(2022-ZJ-763) （2022-ZJ-763）
