大鼠去神經(jīng)骨骼肌萎縮時肌細胞凋亡信號轉(zhuǎn)導通路與MyoD-myogenin表達變化.pdf

1、復旦大學博士學位論文大鼠去神經(jīng)骨骼肌萎縮時肌細胞凋亡信號轉(zhuǎn)導通路與MyoDmyogenin表達變化姓名：吳朝暉申請學位級別：博士專業(yè)：病理學與病理生理學指導教師：金惠銘2001.5.1■，2001年復旦大學醫(yī)學院罅士研究生畢業(yè)論文StudyonapoptoticsignaltransductionpathwayandchangesofMyoD／myogeninexpressioninmuscularatrophyinducedbybra

2、chialplexusinjuryAbstract’Toexplorethemechanismofmuscularatrophyinducedbybrachialplexusinjurywestudiedapoptoticsignaltransductionandmyoblastdifferentiation“theeffectsandmechanismofclenbuterol，creatineandextractofGinkgobi

3、lobainretardingmuscularatrophyinducedbydenervationwereinvestigatedDNAmicroarraywasusedtosearchtherelatedunknowngenetomuscularatrophyTheanimalmodelsofskeletalmuscleatrophywereestablishedinratsbycuttingoffbrachialplexusofo

4、neforelimbThemusclewetweight，forelimbcircumferenceandtotalproteinamountwereusedtomeasurethemuscularatrophyWedetectedthechangesofproteinandmRNAexpressionswithWesternblot／immunohistochemistryandNorthernblot／RT—PERrespectiv

5、elyItwasfoundthattheapoptoticcellspercentagewashigherinatrophicmusclethaninnormalmuscleTheexpressionofapoptosisrelatedgenesuchasFas，F(xiàn)ADD，Casapse一8andCaspase一3increasedsignificantlyinatrophicmuscleTheinhibitorofCaspase一3c

6、oulddecreasetheapoptoticcellspercentageofatrophicmuscleandamelioratethemuscularatrophyTheexpressionofMyoD，myogenin，P21decreasedinatrophicmuscleThecellsofG1phaseandMphasedecreasedwhilethecellsofSphaseincreasedsignificantl

7、yItwasfoundthatclenbuterol，creatineandextractofGinkgobilobacouldretardthemuscularatrophyTheycouldinhibittheexpressionofFasandCaspase一8，anddecreasethepercentageofapoptosisinatrophicmuscleItalsoshowedthatthesedrugscouldup—

8、regulatetheexpressionofMyoDandmyogeninByscanningwithDNAmicroarrayitwasfoundthat17genesexpressedhigherand131genesexpressedlowerinatrophicmusclethanthatinnormalmuscleWeconcludethatbothincreaseofapoptosisanddecreaseofmyobla

9、stdifferentiationplayedimportantrolesinmuscularatrophyinducedbybrachialplexusinjuryFas—FADD—Caspase一8_Caspase一3maybeoneoftheapoptoticsignaltransductionpathwaysThedecreaseofP21promotStheapoptosis，inotherhanditinhibit$thee

10、riectofMyoDtopromotemyoblastdifferentiationTheretardingmechanismofclenbuterol，creatineandextractofGinkgobilobatsrelatedtoinhibitionofapoptosisandaccelerationofmyoblastdifferentiationTheresultsofDNAmicroarrayindicatethatn

11、otonlyapoptosisbutalsootherfactors，suchasthedysfunctionofmitochondria，obstacleofenergeticmetabolism，playimportantrolesinmuscularatrophyKeywords：muscularatrophyapoptosisdifferentiationDNAmicroarrayClassificationNo：R3632R6