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Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats

Acta Pharmacologica Sinica 2006年第5期27卷 527-535页

作者： LLian LI~2 Li-ke ZHANG~5 Yong-zheng PANG~(2.4) Chun-shui PAN~(3.4) Yong-fen QI~(3.4) Li CHEN~4 Xian WANG~(3,4) Chao-shu TANG~(3,4) Jing ZHANG~(2,4,6) ~2Institute of Cardiovascular Research,Peking University First Hospital,Beijing 100034,China:~3Department of Physiology and Pathophysiology,Peking University Health Science Center,Beijing 100083,China ~4Key Laboratory of the Ministry of Education on Molecular Cardiology,Beijing 100083,China:~5Department of Pathophysiology,Capital University of Medicine,Beijing 100054,China lnstituteofcardiovascularresearch PekingUniversityFirstHospitalBeijing100034China DepartmentofPathophysiology CapitalUniversityofMedicineBeijing100054China

Aim:To determine the cardioprotective action of ghrelin and des-octanoyl ghrelinin rats with isoproterenol-induced myocardial ***:Rats were subcu-taneously injected with isoproterenol （ISO;20,10,and 5 mg/kg） on d 1,2 and 3,respectively,and then 3 mg/kg for the next 7d with or without ghrelin or des-octanoyl-ghrelin （100μg/kg,twice daily）.Plasma ghrelin and growth hormonelevels were assayed using radioimmunoassay *** hormone secreta-gogue receptor （GHSR） and ghrelin mRNA were determined using *** binding capacity and the affinity for [3H]ghrelin were determined by re-ceptor binding ***:Compared with controls,ISO-treated rats showedsevere myocardial injury,cardiomegaly,infarction-like necrosis and massive fi-brosis with increases in irradiated-ghrelin （ir-ghrelin） content in plasma by 67%and myocardia by 66% and in the mRNA level in the myocardia by 93% （P<0.01）.ISO-treated rats had 95% （P<0.01） higher GHSR mRNA levels in the *** maximal binding capacity of [3H]ghrelin for myocardial sarcolemma was higherin ISO-treated rats than in *** administration improved cardiac func-tion and ameliorated cardiomegaly and attenuated myocardial lipid peroxidationinjury and relieved cardiac fibrosis as compared with ISO treatment ***-istration of des-octanoyl ghrelin effectively antagonized ISO-induced myocardialinjury and improved all parameters ***,the therapeutic effect ofdes-octanoyl ghrelin was significantly weaker than that of *** plasmagrowth hormone level increased markedly,by 1.5-fold （P<0.01）,with ghrelinadministration as compared with that in controls,but was unaltered in the des-octanoyl ghrelin ***:Myocardial ghrelin and GHSR were up-regulated during ISO-induced myocardial *** protective effect of ghrelinagainst ISO-induced cardiac function injury and fibrosis was more potent thanthat of des-octanoyl ghrelin,which suggests that ghrelin could be an endog

关键词： ghrelin des-octanoyl ghrelin myocardium fibrosis isoproterenol

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