长期体外反搏对高胆固醇血症猪血管内皮细胞的保护作用及机制  

Protective effects and mechanisms of long-term external counterpulsation on endothelial cell in hypercholesterolemia pig

作　　者：何小洪[1] 张焰[1] 陈小林[1] 郑振声[1] 詹澄扬[1] 柳俊[1] 伍贵富[1] 方典秋[1] 梁陆光[1] 钱月桃[1] 凌桂芳[1] 戴刚[1] 冯铭喆[1] 马虹[1] 王奎健[1] 朱振宇[2] 

机构地区：[1]中山大学附属第一医院卫生部辅助循环重点实验室,广州510089 [2]中山大学中山医学院生化教研室

出　　处：《中国康复医学杂志》2005年第10期730-733,T0002,共5页Chinese Journal of Rehabilitation Medicine

基　　金：国家十五攻关课题基金资助项目(2001BA706B07);国家自然科学基金资助项目(50113-4103048)

摘　　要：目的:探讨体外反搏对高胆固醇血症猪血管内皮细胞的保护作用及机制。方法:选雄性乳猪12头用高脂喂养建立动脉粥样硬化模型,对模型猪进行32h体外反搏治疗。用cDNA基因芯片对猪的动脉血管内皮细胞基因表达谱进行量化分析。结果:腹主动脉苏丹Ⅲ染色图像定量分析,高脂组:7.84%±2.37%;高脂加反搏组:1.26%±0.36%。两组差异有显著性意义(P<0.05)。冠状动脉左旋支内膜1:500扫描电镜显示:高脂+反搏组内膜的血管内皮细胞排列有序,细胞呈梭型排列与血流方向一致,表面光滑;高脂组血管内膜细胞排列紊乱,表面不光滑,有大量脱落细胞。显著改变的基因:芯片1(反搏组Cy3/高脂组Cy5):锌指蛋白0.33、MAP4K30.13、长链脂肪酸合成酶0.35、神经介素B受体0.19、GPX-13.26、整合素β10.06、CTGF0.28、eNOS3.1、VCAM-10.50;芯片2(高脂组Cy3/正常组Cy5):锌指蛋白23.06、MAP4K36.75、长链脂肪酸合成酶2.71、神经介素B受体6.68、GPX-10.63、整合素β16.29、CTGF2.45。结论:长期体外反搏可以改善内皮形态与功能,增加内皮细胞抗氧化作用,下调内皮细胞机械性刺激感应蛋白基因的表达,降低血管內皮细胞对LDL的摄取,及下调炎症因子相关基因的表达,起到抗动脉粥样硬化的作用。Objective： To evaluate the efficacy of external eounterpulsation for prevention of atherosclerosis in hyperchnlesterolemia pig.Method：12 male infant pigs were fed with hypercholesterol diet to induce atherosclerosis. These model pigs were received ECP for 32h. The gene expression levels of ECP on endothelial cells were anal- ysed by using cDNA microarray hybridizatinn.Result：The ratios of sudan Ⅲ area in celiac arota were 1.26%±0.36% and 7.84%±2.37% in ECP group and hypercbnlesterolemia group, respectively（P〈0.05）. Scanning electron microscope showed that the endothelial cells in coronary artery were aligned in the direction of blood flow in ECP group and disordered in hypercbolesterolemia group. The significant changes of gene expression in microarray 1：zinc finger protein 0.13, MAP4K3 0.33, long-chain fatty acid coenzyme A ligase5 0.35, neuromedin B receptor 0.19, integrinsβ1 0.06, CTGF 0.28, GPX-1 3.26,eNOS 3.10, VCAM-1 0.50; in mieroarry 2：zinc finger protein 23.06, MAP4K3 6.75 long-chain fatty acid eoenzyme A ligase5 2.71, neuromedin B receptor 6.68, integrinsβ1 6.29, CTCF 2.45, CPX-1 0.63.Conclusion： 32h ECP may reverse endothelial dysfunetion in hypercholesternlemia pigs, downregulate the gene expression of mechanosensing protein in endothelial cell membrane, reduce LDL uptake and inflammatory factors and increase antioxidants in endothelial cells. The changes of gene expression in endothelial cells suggested that ECP may reduce the trend of atherosclerosis.

关 键 词：体外反搏 高胆固醇血症 基因芯片 

分 类 号：R543.3[医药卫生—心血管疾病]