急性药物性内耳损伤中cav1 3钙通道及三种细胞凋亡因子的检测及变化-detection and changes of ca v1 3 calcium channel and three apoptosis factors in acute drug-induced inner ear injury.docx

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2018-05-28 发布于上海
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急性药物性内耳损伤中cav1 3钙通道及三种细胞凋亡因子的检测及变化-detection and changes of ca v1 3 calcium channel and three apoptosis factors in acute drug-induced inner ear injury.docx

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急性药物性内耳损伤中cav1 3钙通道及三种细胞凋亡因子的检测及变化-detection and changes of ca v1 3 calcium channel and three apoptosis factors in acute drug-induced inner ear injury

ABSTRACTObjectiveToinvestigatetheexpressionofCaV1.3calciumchannelproteinandthreeapoptoticfactors(cyt-c,caspase-3,p53)ininnerearwhichisdamagedbyco-administrationofkanamycinandfurosemide.Toanalyzetherelationshipbetweenapoptosisandototoxicity.MethodsC57BL/6Jmiceof4weeksoldwereselectedasexperimentalsubjectswhichwererandomlydividedintoexperimentalandcontrolgroups.Experimentalmiceweredeafenedbyco-administrationofkanamycinandfurosemideandcontrolmiceweregivennormalsalineinjection.Theauditorybrainstemresponse(ABR)wasmeasuredbeforetheadministrationofthedrugsandaweekafter.Reversetranscriptionpolymerasechainreaction(RT-PCR)wasusedtodetectthelevelofCaV1.3mRNAincochleaofC57BL/6Jmiceinthetwodifferentgroups.TheexpressionofCaV1.3,CytochromeC,caspase-3andp53wereassessedandverifiedbyimmunohistochemistricalexamination.Thedifferenceofexpressionwascomparedinthetwogroups.ResultsThemeanvalueforABRthresholdsinresponseoftheexperimentalgroupwassignificantlyincreasedcomparedwiththecontrolgroup.Thedifferencebetweenthetwogroupswasstatisticallysignificant(P0.001).CaV1.3mRNAexpressionwasdecreasedintheexperimentalgroupcomparedwiththecontrolgroup.CaV1.3calciumchannelproteinwasfoundmainlyinthestriavascularis,spiralligament,spiralconvex,haircells,etc.,whoseexpressionwassignificantlydecreasedafterthetreatment.CytochromeC,caspase-3,p53wasfoundmainlyinthestriavascularis,spiralligament,spiralconvex,andhaircells;anditsexpressionwassignificantlyincreasedintheexperimentalmicethaninthecontrolgroup.ConclusionApplicationofkanamycincombinedfurosemidecancauseacutecochlearlesionandhearingdeclineinmice.Thisdrug-inducedototoxicitywassignificantlycorrelatedwiththedamageofCaV1.3calciumchannelproteinandtheapoptosisofhaircells,striavascularis,andspiralganglionneuronintheinnerear.【keywords】C57BL/6Jmice;Aminoglycosideantibiotics;CaV1.3;apoptosis独创性声明本人声明所呈交的学位论文是我个人在导师指导下进行的研究工作及取得的研究成果。尽我所知，除文中已经标明引用的内容外，本论文不包含任何其他个人或集体已经发表或撰写过的研究成果。对本文的研究做出贡献的个人和集体，均已在文中以明确方式标明。本人完全意识到，本声明的法律结果由本人承担。学位论文作者签名：日期：年月日学位论文版权使用授权书本学位论文作者完全了解