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1、中国科技论文在线http://www.paper.edu.cnOBBR对D-GaIN/LPS诱导的急性肝损伤的保护作用及其机制#向红梅1,柴芳妮1,王越1,韩玉龙1,李学刚2,叶小利1**5(1.西南大学生命科学学院,重庆400715;2.西南大学药学院,重庆400715)摘要:急性肝损伤是伴随着高死亡率的一种临床综合征。本文旨在探究8-辛基小檗碱(OBBR)对D-氨基半乳糖/脂多糖(D-GalN/LPS)诱导的急性肝损伤的保护作用及其分子机制。老鼠连续灌胃OBBR七天(15和30mg/kg.day),末次给药后1h,腹腔注射D-GalN/LPS诱导急性肝
2、10损伤。四小时后处死老鼠,收集血清和肝脏备用。结果表明,OBBR降低了血清中丙氨酸转移酶(ALT)和天冬氨酸转氨酶(AST)活性以及肿瘤坏死因子a(TNF-a)、白介6(IL-6)和c反应蛋白水平(CRP)的水平;OBBR促进了肝脏中谷胱甘肽-S转移酶(GSH)的表达并降低了丙二醛(MDA)的产生;OBBR降低了肝脏中TNF-a和IL-6在mRNA和蛋白质水平的表达。此外,OBBR抑制了TLR4、ERK、p38、JNK和NF-kB蛋白在肝脏中的表达。结果表明OBBR15可通过抑制TLR4信号通路来缓解D-GalN/LPS诱导的急性肝损伤。关键词:OBBR
3、;抗炎;抗氧化;急性肝损伤;TLR4中图分类号:Q7ProtectiveeffectofOBBRagainstD-GaIN/LPS-induced20ALFanditsmechanismsXianghongmei1,Chaifangni1,Wangyue1,Hanyulong1,Lixuegang2,Yexiaoli1(1.SchoolofLifeScience,Southwestuniversity,Chongqing400715;2.SchoolofPharmaceuticalSciences,southwestuniversity,Chongqing
4、400715)Abstract:Acuteliverfailure(ALF)isadramaticclinicalsyndromeaccompanyinghighmortality25clinically.Inpresentstudyweaimedtoinvestigatetheprotectiveeffectsandmolecularmechanismsof8-ococtylberberine(OBBR)onALFinducedbyD-galactosamine/Lipopolysaccharide(D-GalN/LPS).Miceweregivenan
5、oraladministrationofOBBR(15and30mg/kgday)for7consecutivedays.AfterthelastadministrationofOBBR,ALFofmicewasinducedbyintraperitoneallyinjectingD-GalN(400mg/kg)/LPS(500μg/kg).Andmiceweresacrificed4hafterreceivingD-GalN/LPS.Theresults30indicatedthatOBBRsignificantlydecreasedtheactivity
6、ofalaninetransferase(ALT)andaspartatetransaminase(AST)inserun,attenuatedthelevelsofcytokines(TNF-a,IL-6andCRP)inserum,markedlyattenuatedlivertheelevationinMDAcontentandimprovedthereductionofglutathione(GSH)intheliverofD-GalN/LPS-inducedALFmice.Besides,OBBRdecreasedthemRNAandprotei
7、nexpressionofcytokines(TNF-aandIL-6)andinhibitedproteinexpressionlevelsofphosphorylatedp38,35JNK,ERKandnuclearfactorkB(NF-kB)intheliver.Keywords:OBBR;Anti-inflammatory;Antioxidant;acuteliverfailure(ALF);Toll-likereceptor40引言肝脏是是人体内最大的新陈代谢器官。酒精中毒、药物中毒和病毒感染等各种原因会引40起急性肝损伤[1]。目前,除了肝移
8、植没有有效的治疗急性肝损伤的方法,因此,寻找有效的治疗方法尤为重要