论文部分内容阅读
Aim:To determine the cardioprotective action of ghrelin and des-octanoyl ghrelinin rats with isoproterenol-induced myocardial injury.Methods: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 methods.Growth hormone secreta-gogue receptor (GHSR) and ghrelin mRNA were determined using RT-PCR.Themaximal binding capacity and the affinity for [~3H]ghrelin were determined by re-ceptor binding assays.Results: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 myocardia.The maximal binding capacity of [~3H]ghrelin for myocardial sarcolemma was higherin ISO-treated rats than in controls.Ghrelin administration improved cardiac func-tion and ameliorated cardiomegaly and attenuated myocardial lipid peroxidationinjury and relieved cardiac fibrosis as compared with ISO treatment alone.Admin-istration of des-octanoyl ghrelin effectively antagonized ISO-induced myocardialinjury and improved all parameters measured.However,the therapeutic effect ofdes-octanoyl ghrelin was significantly weaker than that of ghrelin.The 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 group.Conclusion:Myocardial ghrelin and GHSR were up-regulated during ISO-induced myocardial injury.The 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-enous cardioprotective factor in ischemic heart disease,and that its effects in-clude growth hormone-dependent and-independent pathways.
Aim: To determine the cardioprotective action of ghrelin and des-octanoyl ghrelinin rats with isoproterenol-induced myocardial injury. Methods: Rats were subcu-taneously injected with isoproterenol (ISO; 20, 10 and 5 mg / kg) and 3, respectively, and then 3 mg / kg for the next 7d with or without ghrelin or des-octanoyl-ghrelin (100 μg / kg, twice daily) .Plasma ghrelin and growth hormonelevels were assayed using radioimmunoassay methods. Growth hormone secreta-gogue receptor (GHSR) and ghrelin mRNA were determined using RT-PCR. The maximal binding capacity and the affinity for [~ 3H] ghrelin were determined by re-ceptor binding assays. Results: Compared with controls, ISO-treated rats showed vascular 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) -treated rats had 95% (P <0.01) higher GHSR 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 func- tion and ameliorated cardiomegaly and attenuated myocardial lipid peroxidation in jury and relieved cardiac fibrosis as compared with ISO treatment alone. Admin- istration 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. 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 group. Confc: Myocardial ghrelin and GHSR were up-regulated during ISO-induced myocardial injury. The 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 en endog-enous cardioprotective factor in ischemic heart disease, and that its effects in-clude growth hormone-dependent and-independent pathways.