大鼠去神經(jīng)骨骼肌萎縮時(shí)肌細(xì)胞凋亡信號(hào)轉(zhuǎn)導(dǎo)通路與MyoD-myogenin表達(dá)變化.pdf

1、復(fù)旦大學(xué)博士學(xué)位論文大鼠去神經(jīng)骨骼肌萎縮時(shí)肌細(xì)胞凋亡信號(hào)轉(zhuǎn)導(dǎo)通路與MyoDmyogenin表達(dá)變化姓名：吳朝暉申請(qǐng)學(xué)位級(jí)別：博士專業(yè)：病理學(xué)與病理生理學(xué)指導(dǎo)教師：金惠銘2001.5.1■，2001年復(fù)旦大學(xué)醫(yī)學(xué)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