Ghrelin改善ApoE^(-/-)小鼠心肌梗死后内皮功能和斑块稳定性  

Ghrelin improves endothelial function and plaque stability after myocardial infarction in ApoE^(-/-)mice

作　　者：王丽[1] 庞俊 陈庆伟[1] 李桂琼[1] 柯大智[1] 李兴升[1] WANG Li;PANG Jun;CHEN Qing-wei;LI Gui-qiong;KE Da-zhi;LI Xing-sheng(Department of Geriatrics,the Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China)

机构地区：[1]重庆医科大学附属第二医院老年病科,重庆400010

出　　处：《基础医学与临床》2021年第7期935-940,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(31600957,31871182);重庆市中医药科研项目(ZY20150244)。

摘　　要：目的探讨ghrelin对ApoE敲除(ApoE^(-/-))小鼠心肌梗死后内皮功能和斑块稳定性的影响及机制研究。方法将ApoE^(-/-)小鼠分为对照组、双模型组和ghrelin干预组。所有ApoE^(-/-)小鼠均高脂饮食喂养12周诱导动脉粥样硬化易损斑块,构建的动脉粥样硬化易损斑块模型即为对照组。在第8周时,双模型组和ghrelin干预组结扎冠状动脉左前降支构建急性心肌梗死(AMI)模型。在AMI造模后,ghrelin干预组腹腔注射ghrelin(100μg/kg,2次/d),直至第12周实验结束。对小鼠体质量、血脂进行检测;采用超声心动图检测左心室射血分数(LVEF)和左心室短轴缩短率(LVFS);Griess法检测一氧化氮(NO)水平;采用HE染色观察主动脉斑块面积占管腔面积的百分比;采用油红0和苦味酸天狼猩红染色观察斑块内脂质和胶原的分布;应用RAM-11及β-actin免疫组化染色分别测定斑块内巨噬细胞、平滑肌细胞的分布,计算易损指数;采用Masson染色法检测心肌梗死面积;实时荧光定量PCR和Western blot分别检测血管内皮细胞生长因子(VEGF)mRNA和蛋白表达。结果与对照组相比,双模型组LVEF和LVFS、血清NO2-/NO3-水平降低(P<0.05),VEGF的表达增加(P<0.05)。Ghrelin干预后可显著降低双模型组血浆三酰甘油(TG)水平和心肌梗死面积(P<0.05),升高射血分数(EF)、短轴缩短率(FS)、血浆NO2-/NO3-水平及VEGF的表达(P<0.05),增加斑块内胶原纤维和平滑肌细胞的分布(P<0.05),降低主动脉窦粥样斑块面积的百分比、及斑块内脂质和巨噬细胞的分布(P<0.05),减低易损指数(P<0.05)。结论1)Ghrelin可改善ApoE^(-/-)小鼠心肌梗死后血管内皮功能、提高心功能;2)Ghrelin可促进易损斑块的稳定性,减少再梗死发生。Objective To investigate the effects and mechanisms of ghrelin on plaque stability and endothelial funtion in ApoE^(-/-)mice after myocardial infarction.Methods The ApoE^(-/-)mice were divided into control group,double model group and ghrelin-treated group.All ApoE^(-/-)mice were fed with a high-fat diet for 12 weeks to induce atherosclerotic vulnerable plaques.The atherosclerotic vulnerable plaque model was the control group.At the 8th week of this study,the double model group and the ghrelin group were subjected to acute myocardial infarction model(AMI).After modeling of AMI,the ghrelin group was administered with ghrelin(100μg/kg,bid)until the end of the 12th week.Body weight and blood lipids were detected.Left ventricular ejection fraction(LVEF)andleft ventricular fractional shortening(LVFS)were recorded by echocardiography;NO level was measured by Griess method;the percentage of aortic sinus plaque area was evaluated by HE microscopy.The plaque content of lipid and collagen was observed by Oil Red 0 and Sirius red staining;The distribution of macrophages and smooth muscle cells in plaques were determined by RAM-11 andα-actin immunohistochemical staining and microscopy;And then the vulnerability index was calculated;Myocardial infarct size was measured by Masson staining and microscopy;The vascular endothelial growth factor(VEGF)was detected by quantitative real-time PCR and Western blot.Results Compared with the control group,the level of LVEF and LVFS and NO2-/NO3-concentration in the double model group were all decreased(P<0.05),and the expression of VEGF was increased(P<0.05),significantly.However,the ghrelin group had significantly reduced plasma TG level and also the myocardial infarct size(P<0.05),LVEF,LVFS,NO2-/NO3-level,the expression of VEGF,and the plaque content of collagen and smooth muscle cells were all increased(P<0.05),and reduced the percentage of aortic sinus plaque area,the distribution of lipid and macrophages(P<0.05),and the vulnerability index as compared with the double model group(P

关 键 词：GHRELIN 易损斑块 心肌梗死 内皮功能 ApoE^(-/-)小鼠 

分 类 号：R541.4[医药卫生—心血管疾病]