EVA1A过表达通过调节脂质代谢和促进脂滴自噬改善非酒精性 脂肪肝

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Abstract：ObjectiveToinvestigatetheroleoftransmembraneproteinEVA1Ainliverlipidmetabolismanddevelopmentof non-alcoholic fatty liver disease （NAFLD）. Methods Eight-week-old male ob/ob mice were randomized into control group injectedwithAAVnullvectorviathetailvein（AAV-nullgroup）andAAV-EvalagroupinjectedwithrecombinantvectorAAVEvala（n=8）.HepG2cels transfected withthelentiviral vectorLV-EVA1Aorthenullvector were inducedwitholeicacidto constructacellmodelofNAFLD.TheexpresionlevelsofEVA1A，lipidmetabolism-relatedandautophagy-relatedgenesin mouseliversreetectedithqPCR，Westernblotingandimmunoflorescencestiningndlipidcculationin mouseliversand bloodandinthetreatedcels was examined withHEandOilRedOstainingandlipiddetectionkits.Serum levels of ALT，AST， IL-6， IL-1β，and NF- α of the mice were detected， and hepatic lipophagy was observed with transmission electronmicroscopyResults Themouse liversinAAV-Evala groupandLV-EVA1A-transfectedcelsshowedsignificantly increased expression levelsof EVA1A mRNAand protein.The liver weight andcoeficient and lipid deposition of the mice withAAV-Evalainjectionandtriglyceride（TG）contentinLV-EVAA-transfectedcelsweresignificantlydecreased.Themice inAAV-Evalagroupowedgnicantlyuedsutotalolesterol，D-CandH-Cevelsndpaticeels withloweredserumlevelsofALT，AST，IL-6andTNF-α.InbothmouseliversinAAV-EvalagroupandLV-EVAA-trasfected HepG2cellsace-oaboyseattcidtrasportprotenndacylgeolcyseraseepressoal

significantlydecreasedandadiposetriglyceridelipase increased.Hepaticlipophagy，autophagosomenumbers andLC3-II and ATG5 expressionswere enhanced and p62 expressionwaslowered inthemiceinAAV-Evala group and LV-EVA1A-transfected cells. Conclusion EVA1A overexpressionalleviatesfattyliverandinflammation in ob/obmicebyregulatinglipid metabolism-related genes and enhancing lipophagy to promote clearance of accumulatedhepaticlipids.

Keywords： fatty liver; EVA1A; inflammation; lipid metabolism; lipophagy

非酒精性脂肪肝（NAFLD）是一种以肝脂肪变性为特征的疾病谱，包括相对良性的非酒精性脂肪肝（NAFL）以及病情较为严重的非酒精性脂肪性肝炎（NASH）等，而NASH又可进一步发展为肝纤维化、肝硬化甚至是肝细胞癌。（剩余16071字）