Ghrelin抑制大鼠心肌梗死后心室重构

目的:探讨Ghrelin对大鼠心肌梗死后心室重构的影响及其机制。方法:结扎SD大鼠前降支造成急性心肌梗死(AMI)模型,并设假手术组。结扎24h后,存活大鼠给予Ghrelin(100μg/kg)或生理盐水皮下注射,每天两次。4周后,超声心动图和血流动力学方法检测心功能,实时定量PCR检测梗死心肌白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)mRNA表达,Western-blot检测核转录因子-κB(NF-κB)活性。结果:与假手术组相比,AMI模型组左室收缩内径(LVESD)、左室舒张内径(LVEDD)、左室舒张末压力(LVEDP)都明显增加(P<0.01);而左室收缩压(LVSP)、压力变化值最大值(dp/dtmax)、左室短轴缩短率(FS)都显著降低(P<0.01)。与AMI模型组相比,Ghrelin治疗组LVEDP、LVEDD以及LVESD明显变小(P<0.01),而dp/dtmax及FS显著增加(P<0.01)。梗死后心肌IL-1β、TNF-αmRNA表达增强,Ghrelin治疗后IL-1β、TNF-αmRNA表达明显降低(P<0.01)。AMI模型组心肌核蛋白P65表达明显增加,而胞浆蛋白I-κBα含量显著减少(P<0.01),Ghrelin治疗明显降低梗死心肌核蛋白P65表达(P<0.01),同时增加胞浆蛋白I-κBα含量(P<0.01)。结论:Ghrelin能够抑制心肌梗死后心室重构,改善心功能,可能与其抑制炎症介质表达及NF-κB活性有关。

Ghrelin Inhibits Ventricular Remodeling after Myocardical Infarction in Rats

Objective:To investigate the effect and potential mechanism of ghrelin on ventricular remodeling after acute myocardial infarction in rats.Method:Sprague-Dawley rats underwent coronary ligation to induce MI or sham surgey and received rat ghrelin(100μg/kg SC BID) or saline.4 weeks after treatment,echocardiography and hemodynamic examination were performed,mRNA expression of IL-1β and TNF-α were detected by real-time quantitative PCR,and the NF-κB activity was analysised by western-blot.Results:Compared with the sham-operated group,LV systolic dimension,LV diastolic dimension,and LV end-diastolic pressure were increased(P<0.01),while maximal LV dP/dt,LV systolic pressure and fractional shortening was decreased(P<0.01) in MI rats treated with saline.Ghrelin treatment significantly increased(P<0.01) maximal LV dP/dt,fractional shortening and decreased(P<0.01) LV systolic dimension,LV diastolic dimension,and LV end-diastolic pressure.IL-1β and TNF-α mRNA were enhanced after AMI,and ghrelin significantly reduced the mRNAs expression(P<0.01).Compared with the sham-operated group,nucleus P65 protein expression was increased(P<0.01) and cytoplamsic I-κBα protein content was decreased(P<0.01) in the AMI-control group,ghrelin treatment significantly attentuated the changes.Conclusion:Ghrelin could improve cardiac function and inhibite ventricular remodeling;the proinflammatory mediators and NF-κB may involve the process.