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

作　　者：Lian LI Li-ke ZHANG Yong-zheng PANG Chun-shui PAN Yong-fen QI Li CHEN Xian WANG Chao-shu TANG Jing ZHANG 

机构地区：[1]lnstitute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China [2]Department of Pathophysiology, Capital University of Medicine, Beijing 100054, China [3]Key Laboratory of the Ministry of Education on Molecular Cardiology Beijing 100083, China [4]Department of Physiology and Pathophysiology Peking University Health Science Center, Beijing 100083, China

出　　处：《Acta Pharmacologica Sinica》2006年第5期527-535,共9页中国药理学报（英文版）

基　　金：Project supported by the Major State Basic Research Development Program of the People's Republic of China(No G2000-056905);the National Natural Science Foundation of China(No 30470693)

摘　　要：Aim： To determine the cardioprotective action of ghrelin and des-octanoyl ghrelin in rats with isoproterenol-induced myocardial injury. Methods： Rats were subcutaneously 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 7 d with or without ghrelin or des-octanoyl-ghrelin （100 μg/kg, twice daily）. Plasma ghrelin and growth hormone levels were assayed using radioimmunoassay methods. Growth hormone secretagogue receptor （GHSR） and ghrelin mRNA were determined using RT-PCR. The maximal binding capacity and the affinity for [^3H]ghrelin were determined by receptor binding assays. Results： Compared with controls, ISO-treated rats showed severe myocardial injury, cardiomegaly, infarction-like necrosis and massive fibrosis 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 GI-ISR mRNA levels in the myocardia. The maximal binding capacity of [^3H]ghrelin for myocardial sarcolemma was higher in ISO-treated rats than in controls. Ghrelin administration improved cardiac function and ameliorated cardiomegaly and attenuated myocardial lipid peroxidation injury and relieved cardiac fibrosis as compared with ISO treatment alone. Administration of des-octanoyl ghrelin effectively antagonized ISO-induced myocardial injury and improved all parameters measured. However, the therapeutic effect of des-octanoyl ghrelin was significantly weaker than that of ghrelin. The plasma growth hormone level increased markedly, by 1.5-fold （P〈0.01）, with ghrelin administration as compared with that in controls, but was unaltered in the des- octanoyl ghrelin group. Conclusion： Myocardial ghrelin and GHSR were upregulated during ISO-induced myocardial injury. The protective effect of ghrelin against ISO-induced cardiac function injury and fibrosis was more potent than that of des-octanoyl ghrelin, whichAim： To determine the cardioprotective action of ghrelin and des-octanoyl ghrelin in rats with isoproterenol-induced myocardial injury. Methods： Rats were subcutaneously 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 7 d with or without ghrelin or des-octanoyl-ghrelin （100 μg/kg, twice daily）. Plasma ghrelin and growth hormone levels were assayed using radioimmunoassay methods. Growth hormone secretagogue receptor （GHSR） and ghrelin mRNA were determined using RT-PCR. The maximal binding capacity and the affinity for [^3H]ghrelin were determined by receptor binding assays. Results： Compared with controls, ISO-treated rats showed severe myocardial injury, cardiomegaly, infarction-like necrosis and massive fibrosis 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 GI-ISR mRNA levels in the myocardia. The maximal binding capacity of [^3H]ghrelin for myocardial sarcolemma was higher in ISO-treated rats than in controls. Ghrelin administration improved cardiac function and ameliorated cardiomegaly and attenuated myocardial lipid peroxidation injury and relieved cardiac fibrosis as compared with ISO treatment alone. Administration of des-octanoyl ghrelin effectively antagonized ISO-induced myocardial injury and improved all parameters measured. However, the therapeutic effect of des-octanoyl ghrelin was significantly weaker than that of ghrelin. The plasma growth hormone level increased markedly, by 1.5-fold （P〈0.01）, with ghrelin administration as compared with that in controls, but was unaltered in the des- octanoyl ghrelin group. Conclusion： Myocardial ghrelin and GHSR were upregulated during ISO-induced myocardial injury. The protective effect of ghrelin against ISO-induced cardiac function injury and fibrosis was more potent than that of des-octanoyl ghrelin, which

关 键 词：GHRELIN des-octanoyl ghrelin myocardiumfibrosis ISOPROTERENOL 

分 类 号：R542.2[医药卫生—心血管疾病]