利福平和异烟肼肝脏毒性作用及部分机理-hepatotoxic effects of rifampin and isoniazid and some mechanisms.docxVIP

下载本文档

2
0
约4.97万字
约 52页
2018-05-29 发布于上海
举报
版权申诉

利福平和异烟肼肝脏毒性作用及部分机理-hepatotoxic effects of rifampin and isoniazid and some mechanisms.docx

1、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。。
2、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
3、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
4、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
5、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
6、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
7、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

利福平和异烟肼肝脏毒性作用及部分机理-hepatotoxic effects of rifampin and isoniazid and some mechanisms

Isoniazid-andrifampicin-inducedhepatotoxicityanditsmechanismAbstractsBackgroundandobjective：Bothisoniazid(INH)andrifampicin(RIF)arewidelyuseddrugsinantituberculosistherapyrecommendedbyWorldHealthOrganization(WHO)andthemainreasonofacutedrug-inducedliverinjuryinChina.INHandRIFhasbeenknowntobehepatotoxicbuttheinteractionbetweenINHandRIFisstillnotentirelyclear.INH-inducedhepatotoxicitywasassociatedwithINH-inducedhepaticoxidativestressviahepaticCYP2E1metabolism.StarvationupregulatestheexpressionofCYP2E1inliver.However,whetherstarvationaggravateINH-inducedhepatotoxicityisstillnotentirelyclear.ThetreatmentofRIFcombinedINHsignificantlyincreasedhepaticTGandTCH.However,whetherRIForINHaloneaffectslipidmetabolismneedstobefurtherstudied.Thepurposeofthepresentstudywasto(1)theeffectsofstarvationonINH-inducedhepatotoxicity,(2)theeffectsofRIFaloneonhepaticlipidmetabolism,and(3)theefffectsofRIFonINH-inducedoxidativestressinliver.Methods:Thepresentstudyincludesthreeseparateexperiments.(1)TostudyINH-inducedliverinjury,ICRfemalemiceweredividedintotwogroups:thecontrolgroupandtheINHgroup.MicewereorallyadministeredwithsalineorINH(100mg/kg,dissolvedinsaline)dailyforsevenconsecutivedaysandsacrificedat6hafterthelastINHadministration.ToinvestigatetheeffectsofstarvationonINH-inducedliveroxidativestressinmouseliver,miceweredividedintofourgroups:controlgroup,starvationgroup,INHalonegroupandINHplusstarvationgroup.InINHalonegroup,micewereadministeredwithINH(100mg/kg,dissolvedinsaline)dailybygavageforfourconsecutivedays.InINHplusstarvationgroup,micewerestarvedfor12hbeforeINHand6hafterINH.Controlmicereceivedsalineonly.Atsacrifice,themicewerefastedfor6hafterthelastINHadministration.Serumalanineaminotransferase(ALT),aspartateaminotransferase(AST),alkalinephosphatase(AKP)weremeasuredusingstandardclinicalmethods.Liversectionswerestainedwithhematoxylinandeosintoevaluatethehepatichistology.Theglutathione(GSH)wasdeterminedbythemethodofGriffith.Lipidperoxidationwasquantifiedbymeasuringthiobarbituricacid-reac