ghrelin调控神经生长因子信号途径介导心肌梗死后神经重构

目的ghrelin是最近在胃中分离出来的生长激素释放肽受体的内源性配体，在心血管系统显示出了保护效应。本实验探讨了ghrelin对心肌梗死（MI）后大鼠神经重构的影响及其作用机制。方法sD大鼠结扎冠状动脉制作MI模型作为对照组，干预组在手术后第1天开始给予ghrelin皮下注射，剂量为100μg／kg，每天两次。对照组开胸后在冠状动脉下穿线，但不结扎，给予盐水作皮下注射。经过4个星期治疗后，处死动物。检测梗死区及梗死边缘区神经生长因子，神经纤维标志物以及炎症介质的表达，同时用蛋白免疫印迹法检测了核因子KB（NF-KB）蛋白的表达。结果与对照组相比，ghrelin注射明显减少了梗死区及梗死周边区神经纤维标记物生长相关蛋白43（GAP43）及酪氨酸羟化酶（TH）的阳性表达，同时减少了神经生长因子（NGF）的mRNA及蛋白表达。ghrelin还抑制了炎症因子白细胞介素-1β（IL-1β），肿瘤细胞生长因子-α（TNF-α）以及内皮素-1（ET-1）的mRNA表达，而且非梗死区ET-1mRNA表达与NGF蛋白含量成正相关。ghrelin治疗组梗死边缘区NF-KB活性较对照组明显降低。结论Ghrelin干预能够抑制大鼠MI后神经增生，炎症因子及NGF信号途径可能参与其中。

Ghrelin inhibits cardiac neural remodeling after myocardial infarction in rats

Objective Ghrelin is a newly discovered peptide as an endogenous ligand for the growth hormone secretagogue receptor,and has been demonstrated to exert beneficial effect in the cardiovascular system.In the present study,we investigated whether ghrelin administration could inhibit cardiac neural remodeling and sympathetic hyperinnervation after myocardial infarction(MI).Methods Sprague-Dawley rats underwent coronary ligation to induce MI and received rat ghrelin(100μg/kg SC BID)or saline(control).Four weeks after treatment,rats were sacrificed.We examined the expression of nerve growth factor and never markers as well as the mRNA expressions of proinflammatory mediators.We also examined the NF-κB p65 protein and IκBα protein levels by western blot analysis.Results Compared to the control group,ghrelin administration significantly decreased the density of nerve fibers with positive immunostaining for GAP43 and TH,and decreased NGF mRNA and protein levels.Ghrelin also significantly suppressed interleukin-1β,tumor necrosis factor-α,and endothelin-1 mRNA expression,and inhibited NF-κB activation.In the MI rats,the mRNA expression of ET-1 at the non-infarcted zones had a significantly positive correlation with the NGF protein levels.Conclusion Treatment with ghrelin inhibited neural remodeling and sympathetic hyperinnervation,the process may be associated with the inhibition of proinflammatory response and NGF signaling.