Ghrelin对大鼠心肌梗死后血管重构的影响及机制研究  

Influence of Ghrelin on vascular remodeling after myocardial infarction in rats

作　　者：袁明杰[1] 孔彬[1] 权力[1] 胡红耀[1] 王少波[1] 唐艳红[1] 

机构地区：[1]武汉大学人民医院心血管内科,湖北武汉430060

出　　处：《中国医药导报》2013年第25期4-6,9,共4页China Medical Herald

基　　金：湖北省自然科学基金项目(编号2012FFB04417)

摘　　要：目的研究Ghrelin在心肌梗死(MI)后大鼠心肌血管重构中的作用及其可能的机制。方法成年SD雄性大鼠通过结扎冠状动脉前降支制作心肌梗死模型,假手术组开胸后剪开心包腔,但不结扎左前降支。心肌梗死Ghrelin组大鼠皮下注射Ghrelin,2次/d,剂量为100μg/kg;心肌梗死盐水组皮下注射等量的生理盐水,观察4周。利用RT-PCR法检测VEGF mRNA表达,利用蛋白质印迹(Western-blot)法检测各组动物VEGF蛋白的表达,免疫组化法分析新生血管的密度。结果心肌梗死盐水组与心肌梗死Ghrelin组24 h内死亡情况分别为18.0%比16.0%(P>0.05)。术后存活24 h的45只动物进行Kaplan-Meier生存分析显示,心肌梗死盐水组和心肌梗死Ghrelin组28 d生存率为66.1%比81.2%(P>0.05)。与心肌梗死盐水组相比,Ghrelin显著增加梗死边缘区VEGF mRNA(0.65±0.05比0.35±0.03,P<0.05)及VEGF蛋白表达水平(0.75±0.04比0.50±0.03,P<0.05)。与心肌梗死盐水组相比,Ghrelin能显著增加血管α-平滑肌肌动蛋白在心肌梗死部位密度[(6.0±2.1)/mm2比(4.0±1.8)/mm2,P<0.05)和在梗死边缘区密度[(25.0±9.5)/mm2比(15.0±5.7)/mm2,P<0.05)。结论 Ghrelin可通过增加的VEGF表达促进血管生成,从而改善心功能、防止心脏重塑。Ghrelin可望作为心肌梗死后抑制左室重塑一种新的对策。Objective To investigate the effects of Ghrelin on angiogenesis and its possible mechanism inrats with myocardial infarction （MI）.Methods Adult male Sprague-Dawley rats were subjected to MI by ligating the anterior descending coronary artery,Sham animals underwent thoracotomy and pericardiotomy,but not given LAD ligation.The rats were then treated with a subcutaneous injection of Ghrelin （100 μg/kg） （Ghrelin-treated MI group） or saline （saline-treated MI group） for 4 weeks.VEGF protein expression were detected by Western blot.VEGF mRNA expression were detected by real-time quantitative PCR method.Immunohistochemical method was used to analyze the density of the new blood vessels.Results Early mortality （within 24 h） was comparable between the groups,18％ for the saline-treated MI group and 16％ for the Ghrelin-treated MI group （P ＞ 0.05）.The survival rate of the MI mice at 28 days was not statistically different between the saline-treated MI group and the ghrelin-treated MI group （66.1％ vs 81.2％,P ＞ 0.05）.Compared with the saline-treated MI group,Ghrelin significantly increased the VEGF mRNA expression （0.65±0.05 vs 0.35±0.03,P ＜ 0.05） and VEGF protein expression level（0.75±0.04 vs 0.50±0.03,P ＜ 0.05） in peri-infarct areas.Compared with the saline-treated MI group,Ghrelin significantly increased the density of α-SMA positive vessels in the myocardial infarct areas [（6.0±2.1）/mm2 vs （4.0±1.8）/mm2,P ＜ 0.05] and peri-infarct areas [（25.0±9.5）/mm2 vs （15.0±5.7）/mm2,P ＜ 0.05].Conclusion Ghrelin can promote angiogenesis through enhancement of VEGF,which may improve ameliorate cardiac dysfunction and prevent cardiac remodeling.Ghrelin may be a novel strategy for protecting hearts from LV remodeling after MI.

关 键 词：心肌梗死 心室重构 血管重构 GHRELIN 

分 类 号：R541[医药卫生—心血管疾病]