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学科主题临床医学
Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats
Li, L; Zhang, LK; Pang, YZ; Pan, CS; Qi, YF; Chen, L; Wang, X; Tang, CS; Zhang, J
关键词ghrelin des-octanoyl ghrelin myocardium fibrosis isoproterenol
刊名ACTA PHARMACOLOGICA SINICA
2006-05-01
DOI10.1111/j.1745-7254.2006.00319.x
27期:5页:527-535
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]GROWTH-HORMONE ; FIBROSIS ; RECEPTOR ; HUMANS ; HEART ; DYSFUNCTION ; PEPTIDE ; BINDING ; TISSUES
英文摘要

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 mu g/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 [H-3] 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 GHSR mRNA levels in the myocardia. The maximal binding capacity of [H-3]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 up-regulated 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 suggests that ghrelin could be an endogenous cardioprotective factor in ischemic heart disease, and that its effects include growth hormone-dependent and -independent pathways.

语种英语
WOS记录号WOS:000237179100002
引用统计
被引频次:57[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61695
专题北京大学第一临床医学院_心血管内科
作者单位1.Key Lab Minist Educ Mol Cardiol, Beijing 100083, Peoples R China
2.Peking Univ, First Hosp, Inst Cardiovasc Res, Beijing 100034, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100083, Peoples R China
4.Capital Univ Med, Dept Pathophysiol, Beijing 100054, Peoples R China
推荐引用方式
GB/T 7714
Li, L,Zhang, LK,Pang, YZ,et al. Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats[J]. ACTA PHARMACOLOGICA SINICA,2006,27(5):527-535.
APA Li, L.,Zhang, LK.,Pang, YZ.,Pan, CS.,Qi, YF.,...&Zhang, J.(2006).Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats.ACTA PHARMACOLOGICA SINICA,27(5),527-535.
MLA Li, L,et al."Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats".ACTA PHARMACOLOGICA SINICA 27.5(2006):527-535.
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