Evaluation of Skeletal and Cardiac Muscle Function after Chronic Administration of Thymosin β-4 in the Dystrophin Deficient Mouse 英文参考文献.docVIP

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Evaluation of Skeletal and Cardiac Muscle Function after Chronic Administration of Thymosin β-4 in the Dystrophin Deficient Mouse 英文参考文献.doc

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Evaluation of Skeletal and Cardiac Muscle Function after Chronic Administration of Thymosin β-4 in the Dystrophin Deficient Mouse 英文参考文献

EvaluationofSkeletalandCardiacMuscleFunctionafter ChronicAdministrationofThymosinb-4inthe DystrophinDeficientMouse ChristopherF.Spurney1,Hee-JaeCha2,ArpanaSali3,GouriS.Pandey3,EmidioPistilli4,AlfredoD. Guerron3,HeatherGordish-Dressman3,EricP.Hoffman3,KanneboyinaNagaraju3* 1DivisionofCardiology,Children’sNationalMedicalCenter,Washington,DistrictofColumbia,UnitedStatesofAmerica,2DepartmentofParasitologyandGenetics,Kosin University College of Medicine, Amnam-dong, Seo-gu, Busan, South Korea, 3Center for Genetic Medicine Research, Children’s National Medical Center, Washington, DistrictofColumbia,UnitedStatesofAmerica,4PennsylvaniaMuscleInstitute,SchoolofMedicine,UniversityofPennsylvania,Philadelphia,Pennsylvania,UnitedStatesof America Abstract Thymosin beta-4 (Tb4) is a ubiquitous proteinwith many properties relating to cell proliferation and differentiation that promoteswoundhealingandmodulatesinflammatorymediators.WestudiedtheeffectsofchronicadministrationofTb4 ontheskeletalandcardiacmuscleofdystrophindeficientmdxmice,themousemodelofDuchennemusculardystrophy. Female wild type (C57BL10/ScSnJ) and mdx mice, 8–10 weeks old, were treated with 150mg of Tb4 twice a week for 6 months. To promote muscle pathology, mice were exercised for 30 minutes twice a week. Skeletal and cardiac muscle functionwereassessedviagripstrengthandhighfrequencyechocardiography.LocalizationofTb4andamountoffibrosis were quantified using immunohistochemistry and Gomori’s tri-chrome staining, respectively. Mdx mice treated with Tb4 showed a significant increase in skeletal muscle regenerating fibers compared to untreated mdx mice. Tb4 stained exclusivelyintheregeneratingfibersofmdxmice.Althoughuntreatedmdxmicehadsignificantlydecreasedskeletalmuscle strengthcomparedtountreatedwildtype,therewerenosignificantimprovementsinmdxmiceaftertreatment.Systolic cardiacfunction,measuredaspercentshorteningfraction,wasdecreasedinuntreatedmdxmicecomparedtountreated wildtypeandtherewasnosignificantdifferenceaftert