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

打开文本图片集

Abstract：ObjectiveToinvestigatetheregulatoryroleof theNLRP3signalingpathwayinhepatocytepyroptosisin nonalcoholicsteatohepatitis （NASH）underhypoxia.MethodsTwenty-fourmaleC57BL/6micewererandomizedequallyinto hypoxiccontrol（A）ypoxicNASHmodel（B），ypoxicNAH+NP3ihbitor（C）andhypoxicNAH+aspase-tor （D）groups.IngroupsB-D，the mice werefedamethioninecholine-deficient （MCD）dietunder hypoxicconditions （tosimulate a 5000m altitude）for6weeks;themice in groupsCandDreceived intraperitoneal injectionsof therespectiveinhibitors every otherday.Results Compared withthose in group A，the mice in groupBshowed significantly elevatedserum levelsof FBG， TC，TG，Adeadlrldntlorellidllageeoiod hepatic expressinsofNRP3，caspase-1，IL-1βandGDproteis，withbviousswelingcstaebreakagevacuozatio and outer membrane disruptionofthemitochondria，ribosome loss in the cytoplasm，destructionofthenuclear membrane， and pathologicalchangesoftheroughendoplasmic reticulum.TreatmentwithNLRP3inhibitorandcaspase-1inhibitorboth significantlyloweredseumevelsofTC，G，ALndAbutwithoutsigniicantlyectingG）intemousemodelsnd reducedliverldentmrcelliioollagpoiodeiolelsf GSDMDand IL-1β.Thetreatments also significantly improved pathological changes inthe mitochondria，ribosomes and endoplasmic reticulum in liver tissues ofthe mice. Conclusion NLRP3 signaling pathway plays a keyrole in promoting hepatocytepyroptosisinNASHmiceunderhypoxiccondition，andinhibitingthispathwaycaneffectivelyreduceliver inflammation， suggesting its potential asa therapeutic target for NASH treatment.

Keywords：hypoxia;nonalcoholicsteatohepatitis;hepatocytepyroptosis;NLRP3inflammatorypathway

非酒精性脂肪性肝病（NAFLD）是一种由于胰岛素抵抗、遗传易感性等因素引起的慢性肝脏损伤性疾病，可进展为非酒精性脂肪性肝炎（NASH）肝硬化甚至肝癌2。（剩余13212字）