Hexarelin Treatment in Male Ghrelin Knockout Mice after Myocardial Infarction
Hexarelin Treatment in Male Ghrelin Knockout Mice after Myocardial Infarction
复制标题
DOI：
10.1210/en.2013-1291
复制
发表时间：
2013-10-01
期刊：
影响因子：
4.8
通讯作者：
Kangawa, Kenji
中科院分区：
文献类型：
--
作者：
Mao, Yuanjie;Tokudome, Takeshi;Kangawa, Kenji
据报道，生长素释放肽和合成类似物海沙瑞林都具有主要通过不同受体发挥作用的心脏保护作用。然而，它们对急性心肌梗死的作用尚未在体内进行比较。本研究旨在阐明海沙瑞林治疗是否可以补偿生长素释放肽敲除小鼠的生长素释放肽缺乏，并比较海沙瑞林（400 nmol/kg/d，皮下注射）和等摩尔生长素释放肽治疗心肌梗死后的效果。通过结扎雄性生长素释放肽基因敲除小鼠的左冠状动脉产生心肌梗塞，然后该小鼠接受生长素释放肽、海沙瑞林或媒介物治疗两周。海沙瑞林组 (6.7%) 和生长素释放肽组 (14.3%) 的 2 周内死亡率显着低于媒介物组 (50%) (P < .05)。梗死后 2 周心功能比较显示，在 ghrelin 和海沙瑞林治疗组中，心输出量更大，而以射血分数表示的收缩功能和以 dP/dt min（压力下降峰值速率）表示的舒张功能明显优于载体组 (P < .05)。从射血分数、dP/dt max（压力上升峰值速率）和 dP/dt min 可以看出，Hexarelin 治疗比 ghrelin 治疗更有效。遥测记录和心率变异性分析表明，相对于载体组，海沙瑞林和生长素释放肽组的交感神经活动明显受到抑制。我们的数据表明，在 ghrelin 敲除小鼠心肌梗塞后 2 周，海沙瑞林治疗可以比 ghrelin 治疗产生更好的心脏功能，尽管两种激素对心率变异性和死亡率具有相似的影响。
Both ghrelin and the synthetic analog hexarelin are reported to possess cardioprotective actions that are mainly exerted through different receptors. However, their effects on acute myocardial infarction have not been compared in vivo. This study aimed to clarify whether hexarelin treatment can compensate for ghrelin deficiency in ghrelin-knockout mice and to compare the effects of hexarelin (400 nmol/kg/d, sc) and equimolar ghrelin treatment after myocardial infarction. Myocardial infarction was produced by left coronary artery ligation in male ghrelin-knockout mice, which then received ghrelin, hexarelin, or vehicle treatment for 2 weeks. The mortality within 2 weeks was significantly lower in the hexarelin group (6.7%) and ghrelin group (14.3%) than in the vehicle group (50%) (P < .05). A comparison of cardiac function 2 weeks after infarction showed that in the ghrelin and hexarelin treatment groups, cardiac output was greater, whereas systolic function, represented by ejection fraction, and diastolic function, represented by dP/dt min (peak rate of pressure decline), were significantly superior compared with the vehicle group (P < .05). Hexarelin treatment was more effective than ghrelin treatment, as indicated by the ejection fraction, dP/dt max (peak rate of pressure rise), and dP/dt min. Telemetry recording and heart rate variability analysis demonstrated that sympathetic nervous activity was clearly suppressed in the hexarelin and ghrelin groups relative to the vehicle group. Our data demonstrated that hexarelin treatment can result in better heart function than ghrelin treatment 2 weeks after myocardial infarction in ghrelin-knockout mice, although both hormones have similar effects on heart rate variability and mortality.