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1、显著增加（p<0.05）。根据上述实验结果，我们认为用于治疗老年痴呆的乙酰胆碱酯酶抑制剂不加重对乙酰氨基酚所致肝损伤，而对其具有保护作用；乙酰胆碱酯酶抑制剂对对乙酰氨基酚所致肝损伤的保护作用与其抑制中枢乙酰胆碱酯酶活性有关；乙酰胆碱酯酶抑制剂通过M乙酰胆碱受体的激动保护肝脏线粒体功能；并通过间接刺激N乙酰胆碱受体α7亚型，减少促炎细胞因子释放和JNK2磷酸化，从而减轻对乙酰氨基酚所致肝损伤。关键词乙酰胆碱酯酶抑制剂；对乙酰氨基酚；肝损伤；线粒体损伤；胆碱能抗炎通路III万方数据AbstractThepresentstudywasdesigne
2、dtoevaluatetheeffectandmechanismofacetylcholinesteraseinhibitor(AChEI)onliverinjuryinducedbyacetaminophen(APAP)inmice.LiverinjurywasinducedbytreatmentofAPAP(300mg/kg).1.MaleC57BL/6Jmicewererandomlydividedintoeightgroups:controlgroup,APAPgroup,HupA(0.2mg/kg)group,Don(4mg/kg)
3、group,Riv(2mg/kg)group,APAP+HupAgroup,APAP+DongroupandAPAP+Rivgroup.ThemiceincontrolgroupandAPAPgroupwereadministeredwithnormalsalineand0.5%(w/v)sodiumcarboxymethylcellulose.HupA,DonandRivweregivenintragastricallyinavolumeof0.2mL/10gbodyweighteveryday.Miceweretreatedforcons
4、ecutive4daysandfastedaftertreatmentinthethirddayfor16hbuthadfreeaccesstowaterbeforeAPAPinjection.Theacetylcholinesterase(AChE)activityinbloodandbrain,theaspartateaminotransferase(AST)andalanineaminotransferase(ALT)activityinserumaswellasthepathologicalchangesoftheliverwered
5、etermined.2.TostudytheprotectivemechanismofAChEIonAPAPinducedliverinjury.(1)Micewererandomlydividedintotengroups:controlgroup,APAPgroup,HupAgroup,Dongroup,Rivgroup,Neo(0.15mg/kg)group,APAP+HupAgroup,APAP+Dongroup,APAP+RivgroupandAPAP+Neogroup.ThemiceincontrolgroupandAPAPgro
6、upwereadministeredwith0.5%(w/v)sodiumcarboxymethylcelluloseandnormalsaline.Neowasadministratedintraperitonealinadoseof0.1mL/10gbodyweighteveryday.Miceweretreatedforconsecutive4daysandfastedaftertreatmentinthethirddayfor16hbuthadfreeaccesstowaterbeforeAPAPinjection.TheAChEac
7、tivityinbloodandbrain,theALT,ASTactivityinserumaswellasthepathologicalchangesoftheliverweredeterminedinallgroups.(2)Miceinthe1sttestwereutilizedtoinvestigatetheGSHcontentandCYP2E1activityinliver.(3)MicewererandomlyIV万方数据dividedintothirteengroups:controlgroup,APAPgroup,HupAg
8、roup,Rivgroup,Atrgroup,Mecgroup,MLAgroup,Atr+HupAgroup,Atr+Rivgroup,Mec+HupAgroup,
