RelationshipbetweenthemechanismofAMPK-mediatedmyocardialmitochondrialautophagyandTSC2indiabeticrats

Abstract:

Objective：ToinvestigatetherelationshipbetweenthemechanismofAMP-activated-protein-kinase（AMPK）-mediatedmyocardialmitochondrialautophagyandtuberoussclerosiscomplex-2（TSC2）indiabeticrats.Methods：ThirtyadultmaleSDratswererandomlydividedintocontrolgroup，modelgroup，andmodelgroup+AMPKagonistAICARgroup（AICARgroup）.Thediabeticratmodelwasestablishedbyintraperitonealinjectionofstreptozotocin.RatsintheAICARgroupweresubcutaneouslyinjectedwithAICARfor12weeks.Cardiacfunctionofallratswasmeasuredbyechocardiography，includingleftventricularend-diastolicvolume（LVEDV），leftventricularend-systolicvolume（LVESV），leftventricularejectionfraction（LVEF），heartrate（HR），peakvelocityofearlydiastolicflow（E），peakvelocityoflatediastolicflow（A），andE/A.ThemyocardialtissuewastakentodetectthebindinglevelsofAMPKandTSC2byimmunoprecipitationandtheexpressionlevelsofAMPK，TSC2，p-TSC2，LC3-Ⅱ，LC3-Ⅰ，Beclin-1andP62weredetectedbyWesternblot.Results：ThelevelsofLVEDV，LVEF，EandE/AinAICARgroupwerehigherthanthoseinthemodelgroup，butAwaslowerthanthatinthemodelgroup（P=0.004，P=0.001，P=0.000，P=0.011，P=0.027）.ThelevelsofAMPKandTSC2proteininAICARgroupwerehigherthanthoseinthemodelgroup（0.71±0.06vs.0.36±0.09，P=0.003；0.80±0.02vs.0.40±0.05，P=0.017）.ThebindinglevelofAICARgroupwashigherthanthatinthemodelgroup（0.49±0.09vs.0.23±0.03，P=0.002），andthelevelofp-TSC2proteininAICARgroupwashigherthanthatinthemodelgroup（1.48±0.07vs.0.92±0.07，P=0.029）.ThelevelsofLC3-Ⅱ/LC3-Ⅰ，Beclin-1andP62inAICARgroupwerehigherthanthoseinmodelgroup（P<0.05）.Conclusion：ThemechanismofAMPK-mediatedmyocardialmitochondrialautophagyindiabeticratsmayberelatedtoitsphos－phorylationtoTSC2.