Chang Lin, Zhao Jing, Li Gui-Zhong, Geng Bin, Pan Chun-Shui, Qi Yong-Fen, Tang Chao-Shu
Institute of Cardiovascular Disease Research, the First Hospital Beijing 100034, China.
Acta Pharmacol Sin. 2004 Sep;25(9):1131-7.
To investigate the cardiac protective effects of ghrelin in rat with myocardial injury induced by isoproterenol (ISO).
Rats were subcutaneously injected ISO 40 mg/kg/d with or without ghrelin 1 or 10 nmol/kg/d for 2 d. Hemodynamic parameters including mean arterial blood pressure and left ventricular pressure were measured at 12 h after the last injection with ISO and/or ghrelin. Plasma lactate dehydrogenase (LDH) activity, plasma and myocardial contents of malondialdehyde (MDA), and conjugated diene were measured. Plasma ghrelin and endothelin-1 levels were assayed using radioimmunoassay methods. Endothelin-1 and ghrelin mRNA were determined using RT-PCR.
About 45 % (5/11) of rats after treatment with ISO alone died during experimental periods. However, no rats died after administration with ghrelin 10 nmol/kg/d (0/11, P<0.05). Ghrelin also obviously ameliorated the hemodynamic disturbance in rats induced by ISO. The plasma LDH activity, contents of myocardial and plasma MDA, and conjugated diene level in plasma in ISO+G10 nmol/kg/d group were decreased by 28 %, 34 %, 73 %, and 38 % compared with those of ISO group (all P<0.01) respectively. ISO-induced endothelin-1 mRNA over-expression was inhibited and endothelin-1 level in plasma were inhibited by ghrelin 1 and 10 nmol/kg/d. The ghrelin levels in plasma and ghrelin mRNA in myocardium were increased in the rats after injection of ISO. The plasma ghrelin level was further increased after ghrelin administration.
Ghrelin has a protective effect against ISO-induced myocardial injury.
探讨胃饥饿素对异丙肾上腺素(ISO)诱导的大鼠心肌损伤的心脏保护作用。
大鼠皮下注射ISO 40mg/kg/d,同时或不同时皮下注射胃饥饿素1或10nmol/kg/d,持续2天。在最后一次注射ISO和/或胃饥饿素后12小时测量血流动力学参数,包括平均动脉血压和左心室压力。检测血浆乳酸脱氢酶(LDH)活性、血浆和心肌丙二醛(MDA)含量以及共轭二烯。采用放射免疫分析法测定血浆胃饥饿素和内皮素-1水平。用RT-PCR法测定内皮素-1和胃饥饿素mRNA。
单独用ISO治疗的大鼠约45%(5/11)在实验期间死亡。然而,给予10nmol/kg/d胃饥饿素后无大鼠死亡(0/11,P<0.05)。胃饥饿素还明显改善了ISO诱导的大鼠血流动力学紊乱。与ISO组相比,ISO+G10nmol/kg/d组血浆LDH活性、心肌和血浆MDA含量以及血浆共轭二烯水平分别降低了28%、34%、73%和38%(均P<0.01)。1和10nmol/kg/d胃饥饿素抑制了ISO诱导的内皮素-1mRNA过度表达,并抑制了血浆内皮素-1水平。注射ISO后大鼠血浆胃饥饿素水平和心肌胃饥饿素mRNA增加。给予胃饥饿素后血浆胃饥饿素水平进一步升高。
胃饥饿素对ISO诱导的心肌损伤具有保护作用。