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学科主题: 临床医学
题名:
Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats
作者: 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
发表日期: 2006-05-01
DOI: 10.1111/j.1745-7254.2006.00319.x
卷: 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
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61695
Appears in Collections:北京大学第一临床医学院_心血管内科_期刊论文

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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

Recommended Citation:
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.
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