Ghrelin对多柔比星诱导大鼠心力衰竭和心肌损伤的保护作用及机制

Ghrelin ameliorates doxorubicin⁃induced heart failure and cardiac injury in rats

目的探讨Ghrelin保护盐酸多柔比星诱导的大鼠心力衰竭和心肌损伤的保护作用及机制。方法雄性SD大鼠32只,随机分为对照组、心力衰竭组和Ghrelin组。心力衰竭组和Ghrelin组大鼠给予腹腔注射盐酸多柔比星建立心力衰竭模型。Ghrelin组大鼠给予每天两次腹腔注射Ghrelin,心力衰竭组和对照组大鼠分别给予等容积生理盐水,共持续6周。观察大鼠心脏超声心动图、心脏血流动力学、心肌组织学变化和检测血浆炎症因子及氧化应激指标变化。结果与心力衰竭组大鼠比较,Ghrelin组大鼠左心室收缩末期内径(LVSD)显著降低(P<0.05),左心室射血分数(LVEF)明显增加(P<0.05)。大鼠左心室内压最大上升速率(+dP/dtmax)明显升高(P<0.01)。Ghrelin组大鼠呈现心肌细胞变性和坏死,程度和范围均较心力衰竭组大鼠明显减轻。Ghrelin组血浆肿瘤坏死因子(TNF)⁃α和15⁃F2t⁃isoprostane水平比心力衰竭组明显降低(P<0.01),白细胞介素(IL)⁃10水平明显升高(P<0.05)。结论Ghrelin可能通过调节机体炎症和氧化应激反应减轻多柔比星诱导的大鼠心肌损伤和改善心脏功能。

Objective To investigate the protection of ghrelin against doxorubicin⁃induced heart failure and cardiac injury in rats and underlying mechanisms.Methods A total of 32 Sprague⁃Dawley(SD)rats were randomized into control group,heart failure group and ghrelin group.Rat heart failure was induced by intraperitoneal injection of doxorubicin.The rats with heart failure in the ghrelin group and those in the heart failure and control groups were intraperitoneally injected with ghrelin and the same volume of saline twice per day,respectively.The changes in echocardiographic parameters,cardiac hemodynamics,myocardial histology,plasma levels of TNF⁃α,IL⁃10 and 15⁃F2t⁃isoprostane in the rats were analyzed.Results Compared with the heart failure group,the rats in the ghrelin group had significantly lower LVSD(P<0.05),higher left ventricular ejection fraction(LVEF)(P<0.05)and maximum rise speed of left ventricular pressure(+dP/dtmax)(P<0.01).Histological analysis revealed that the rats in the ghrelin group had lesser cardiomyocyte degeneration and necrosis than those in the heart failure group.Mechanistically,the rats in the ghrelin group had significantly lower plasma levels of TNF⁃αand 15⁃f2t⁃isoprostane(P<0.01),but higher plasma IL⁃10 level(P<0.05).Conclusion Ghrelin improves cardiac function of doxorubicin⁃induced heart failure and ameliorates myocardial injury at least in part through regulating inflammatory response and oxidative stress.