胃促生长素对兔动脉粥样硬化斑块内血管新生的影响及相关机制  

Effects and mechanisms of ghrelin on plaque neovascularization in rabbits with atherosclerosis

作　　者：王丽[1] 李桂琼[1] 陈庆伟[1] 柯大智[1] 

机构地区：[1]重庆医科大学附属第二医院老年心血管科,400010

出　　处：《中华内分泌代谢杂志》2015年第8期717-724,共8页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金（31271262）;重庆市博士后基金（Xm201351）

摘　　要：目的：动脉粥样硬化斑块内血管新生与易损斑块的不稳定与破裂密切相关,本实验观察胃促生长素（ ghrelin）对兔动脉粥样硬化斑块内血管新生的影响及相关机制。方法雄性健康新西兰大白兔30只,随机分为正常对照组、动脉粥样硬化模型组（模型组）及ghrelin干预组,每组10只。采取高脂饮食＋球囊损伤内膜的方法建立动脉粥样硬化模型,ghrelin干预组予ghrelin 25μg·kg-1·d-1耳缘静脉注射,其余2组予等量生理盐水耳缘静脉注射,4周后检测各组体重、血脂（甘油三酯、总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇）,HE染色测量斑块厚度及内膜中膜厚度比,CD31免疫组化染色检测动脉粥样硬化斑块内新生血管生成密度,实时荧光定量PCR和Western印迹法分别检测各组血管内皮细胞生长因子（vascular endothelial growth factor, VEGF）和血管内皮细胞生长因子受体（vascular endothelial growth factor receptor 2, VEGFR2）的mRNA和蛋白表达,免疫组织化学和 Western 印迹检测斑块内基质金属蛋白酶（matrix metalloproteinase, MMP）-2、MMP-9的表达。结果（1）模型组和ghrelin干预组体重和血脂变化均无显著性差异（P〉0.05）,均显著高于正常对照组（P〈0.05）；（2）与模型组相比,ghrelin干预组可减少斑块厚度,并显著降低内膜与中膜厚度之比（P〈0.05）；（3）与模型组相比,ghrelin干预组新生血管计数、VEGF及其受体VEGFR2表达显著减少（P〈0.05）；（4）与模型组相比,ghrelin可显著降低斑块内MMP-2和MMP-9的表达。结论 ghrelin能抑制斑块内血管新生促进易损斑块稳定性,其机制可能与ghrelin显著减少斑块内VEGF和VEGFR2表达,抑制MMP-2和MMP-9的生成有关。Objective The aim of our study was to investigate the effects and mechanisms of ghrelin on neovascularization in atherosclerosis plaque. Methods 30 male New Zealand rabbits were randomly divided into normal control group （ CON group ）, atherosclerosis model group （ AS group ） , and ghrelin treatment group （ ghrelin group） , and each group of 10 rabbits. The AS group and ghrelin group underwent balloon-induced arterial wall injury and then fed with high fat diet, the CON group was fed only on a regular diet. They were all fed for 3 months. Then the ghrelin group was given ghrelin 25 μg · kg-l · d-1 , the other two groups received the same amount of sterile normal saline only. Four weeks later, body weight and blood lipids were detected. The thickness ratio of the intima to media was measured by HE staining. Degree of intra-plaque angiogenesis was evaluated by CD31 ＋ cells immunohisto- chemistry. The vascular endothelial growth factor （VEGF） and vascular endothelial growth factor receptor 2 （VEGFR2） were detected by quantitative realtime PCR and Western blot. The expressions of matrix metalloproteinase （MMP） -2 and MMP-9 were detected by immunohistochemistry and Western blot. Results （ 1 ） No significant differences in body weight and blood lipids were found between the AS group and the ghrelin group （ P〉0.05 ）, but both items were significantly higher than those of the CON group （ P〈0.05 ）. （ 2 ） The thickness ratio of the intima to media in the ghrelin treated group was distinctly less than that in the AS group （ P〈0.05 ）. （ 3 ） Compared with the AS group, the ghrelin group showed significantly decreased microvascular density and the expressions of VEGF and VEGFR2 （ P〈0.05 ）. （4） Compared with the AS group, ghrelin dramatically inhibited the plaque contents of MMP-2 and MMP-9 （ P 〈 0. 05 ）. Conclusions Ghrelin is able to inhibit the growth of neovascularizationin in the atherosclerotic plaque and the development of plaque. And these bene

关 键 词：胃促生长素 血管新生 动脉粥样硬化 斑块稳定性 

分 类 号：R543.5[医药卫生—心血管疾病]