酒精性脂肪肝脂质代谢研究进展.pdfVIP

安 徽 医 药 AnhuiMedicalandPharmaceuticalJournal2012Aug；16(8) ·1045· ◇综述与讲座◇ 酒精性脂肪肝脂质代谢研究进展 胡成穆，曹 琦，李 俊 (安徽 医科大学药学院、安徽天然药物活性研究省级实验室，安徽 合肥 230032) 摘要：酒精性脂肪肝 (AFL)是长期大量饮用酒精引发的肝脏损害性病变，可逆转也可进一步发展为肝纤维化和肝硬化。众多的 脂肪细胞因子如瘦素(Leptin)、抵抗素(Resistin)和肿瘤坏死因子一仪(TNF-0)【在脂肪肝的发病中起到一定的促进作用，脂联素 (Adiponectin)能改善脂质代谢，延缓脂肪肝的发生；脂联素通过腺苷酸活化蛋白激酶(AMPK)调节糖脂代谢、改善胰岛素敏感 性。脂联素／AMPK信号通路是酒精在肝脏的作用靶点、也是调节PPAR~作用的重要信号通路；脂肪分化相关蛋白(ADRP)调 节脂质代谢 、促进酒精性脂肪肝的形成；过氧化物酶增殖体激活受体 ^y(PPAR )参与机体脂质稳态的调节，脂肪肝时PPAR 表 达增高，肝纤维化时PPAR~／表达减少。对酒精性脂肪肝脂质代谢的深入研究，有助于阐明酒精性脂肪肝发病机制并为临床防 治ALD及脂质代谢相关疾病提供新策略。 关键词：酒精性脂肪肝 ；脂肪细胞因子；脂联素；腺苷酸活化蛋白激酶(AMPK)；过氧化物酶增殖体激活受体 _y(PPAR．y) Progressresearchonlipidmetabolicin alcoholicfattyliver HUCheng—mu．CAOQi．LIJun (AnhuiKeyLaboratoryofBioactivityofNaturalProducts，CollegeofPharmacy，AnhuiMedicalUniveni@，Hefei230032，China) Abstract：Alcoholicfattyliver(AFL)isreversiblecondition，butitcanpotentiatethedevelopmentofalcoholichepatitisandevencirrho- sisifalcoholconsumptioniscontinued．Manyadipocytokinessuchasleptin．resistinandTNF-0lhaveanimportantrelationshipwithhe— paticsteatosis，whileadiponectinhasprotectiveeffectonAFL．Adiponectinconfersprotectionagainstalcoholicfattyliverviamodulation ofAMP—activatedproteinkinase(AMPK)．Adiponectin—AMPKisthekeysignaltransductionpathwayinvolvedintheactionofPPAR ag— onistprotectionagainstalcoholicfattyliver．Adiposedifferentiation—relatedprotein(ADRP)couldregulatelipidmetabolismandaggravate theformationofAFL．Overexpressionofperoxisomeproliferator—activatedreceptor (PPAR )maycauseaseriouslipidmetbaolicdis— turbance．WhereasexpressionofPPARyismarkedlyhighinalcoholicfattyliver，expressionofH)AR inalcoholichepaticfibrosisisobviously low．Thisarticlediscussedthemechanismsbywhichalcoholcontributestoincreasinglipidaccumulationintheliver；furtherelucidationof these findingswouldprovideanoveltherapeuticstrategyfortreatingalcoho