心外膜脂肪组织转染人apM1基因抑制兔冠状动脉粥样硬化的形成  

Human apM1 gene transfers into the epicardial adipose tissue to inhibit the formation of coronary atherosclerosis in rabbits

作　　者：杨文凯[1,2] 董念国[1] 陈庆[3] 王现国[1] 谢霆[1] 陈新忠[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院心外科 ,湖北省武汉市430022 [2]华中科技大学同济医学院附属协和医院,湖南省武汉市430022 [3]江西省人民医院胸心外科,江西省南昌市330006

出　　处：《中国组织工程研究》2012年第20期3768-3772,共5页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(30872541);博士点基金新教师项目资助课题(200804871116)~~

摘　　要：背景:心外膜脂肪分泌的脂联素水平下降可能是导致冠状动脉粥样硬化的主要原因之一。目的:观察人脂联素基因apM1转染至兔心外膜脂肪组织对高脂喂食兔冠状动脉粥样硬化形成的影响。方法:向兔心包腔内注射脂质体包裹的pEGFP-apM1重组质粒50μL,分别于注射后2,7,28d观察转染效率。采用高脂喂食方法制备兔冠状动脉粥样硬化模型,并按上述方法转染apM1基因,于转染后4周取材。结果与结论:心包腔内转染apM1基因2d后即可检测到兔心外膜脂肪组织apM1基因高表达,并可持续至28d。心外膜脂肪转染apM1基因对高脂喂食引起的外周血脂联素、肿瘤坏死因子α、总胆固醇、高密度脂蛋白胆固醇及低密度脂蛋白胆固醇水平无显著影响,但可使心包腔液中脂联素水平显著增加、肿瘤坏死因子α水平显著降低(P<0.01),冠状动脉内膜/中膜厚度比减小40.66%。说明经心包腔注射可将apM1基因有效转染入心外膜脂肪组织,并可在局部通过抑制高脂诱导的炎性因子释放而抑制冠状动脉粥样硬化的形成。BACKGROUND： The decreased level of adiponectin secreted from the epicardial adipose tissue may be one of the main reasons leading to coronary atherosclerosis. OBJECTIVE： To investigate the effect of human apM1 gene transferring into the epicardial adipose tissue on the formation of coronary atherosclerosis in high-cholesterol fed rabbits. METHODS： 50 μL mixture of pEGFP-apM1 and liposome was injected into the rabbit pericardial cavity. The epicardial adipose tissue was harvested at 2, 7 and 28 days respectively after injection and was made into fast frozen sections. The transfection efficiency and expression of apM1 were detected by fluorescence microscopy and immunohistochemical method. Twenty-four male New Zealand White rabbits were randomly divided into four groups： normal control group, high-fat group, high-fat plus pEGFP injection group, high-fat plus pEGFP-apM1 injection group. At 4 weeks after injection, the expression of apM1 in epicardial adipose tissue was detected by Western blot analysis. RESULTS AND CONCLUSION： In the rabbit epicardial adipose tissue, the high expression of apM1 was detected at 2 days after injection and until to 28 days. The effective transfection was not detected in the epicardial connective and myocardial tissues. The levels of adiponectin, tumor necrosis factor-α, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol in the peripheral blood changed insignificantly change after pEGFP-apM1 injection into the pericardial cavity. In high-fat plus pEGFP-apM1 injection group, the distinct increase of adiponectin and decrease of tumor necrosis factor-α （P 〈 0.01） were measured in the pericardial cavity fluid. Compared with the high-fat group, pEGFP-apM1 injection could decrease the intima/media ratio of left coronary artery to 40.66%. The apM1 gene could be effectively transferred into the epicardial adipose tissue through the pericardial cavity injection. The increase of adiponectin expression in the epicardial adipose tissue

关 键 词：脂联素 apM1 心外膜脂肪组织 冠状动脉粥样硬化 

分 类 号：R318[医药卫生—生物医学工程]