核因子κB的反义和诱骗性寡核苷酸对大鼠球囊损伤后血管狭窄和新生内膜形成的影响  

Role of the Antisense and Decoy Oligonucleotide of Nuclear Factor-κB in the Vessel Stenosis and Neointima Formation in Balloon-injured Rat Artery

作　　者：周俊[1] 陆国平[1] 戚文航[1] 

机构地区：[1]上海第二医科大学附属瑞金医院心内科,上海市200025

出　　处：《中国动脉硬化杂志》2003年第4期314-318,共5页Chinese Journal of Arteriosclerosis

基　　金：上海市教委重点学科基金 ( 8990 2 0 7)资助

摘　　要：探讨核因子κBp6 5亚基的反义和诱骗性寡核苷酸单独或联合作用对大鼠颈动脉球囊损伤细胞间粘附分子、单核细胞趋化因子的作用。SD大鼠随机分为 7组 ,每组分为 6个时相点 (6h和 1、3、5、7、1 4d) ,每个时相点 3只大鼠。制作血管球囊损伤模型。相应时间点处死动物。模型组、正义组、诱骗对照组血管内膜面积、中膜面积、内膜 中膜在第 5天增加 ,1 4d达到高峰。管腔面积随时相点减小。反义组、诱骗组、反义组 +诱骗组干预后 ,血管上述病理指标明显改善 (P <0 .0 5 ) ,反义组 +诱骗组较反义组、诱骗组治疗效果更明显 (P <0 .0 5 )。内皮细胞间粘附分子、单核细胞趋化因子mRNA表达在血管损伤后 6h即可检测到 ,3、5、7d后持续表达增加 ,1 4d后表达降低。免疫组织化学检测显示 ,内皮细胞间粘附分子 1、单核细胞趋化因子 1蛋白质表达在 6个时相点均为阳性染色 ,1 4d达到高峰 ;反义组、诱骗组、反义组 +诱骗组治疗后 ,与模型组、正义组、诱骗对照组相比 ,内皮细胞间粘附分子、单核细胞趋化因子mRNA表达和蛋白合成在各时相点均降低 (P <0 .0 5 )。免疫印迹法检测核蛋白抽提物显示 ,核因子κBp6 5在血管损伤后 6h有一定蛋白表达 ,1d后蛋白表达明显增加 ,至 7d达高峰 ,1 4d后蛋白表达略降低。反义组、诱骗组。Aim To examine the effect of the antisense or/and decoy oligonucleotide of nuclear factor κB (NF κB) on balloon injured intercellular adhesive molecular 1 (ICAM 1) and monocytes chemotactic protein 1 (MCP 1) in the carotid artery of rats in vivo. Methods Sprague Dawley rats underwent balloon dilation injury of the left carotid artery. Rats was divided into 7 groups (n=18) and each group included 6 time points (6 hours and 1,3,5,7,14 days) (n=3). Uninjured artery of the same rat was used to be control. Results In model group, sense group and scramble group, vessel intima area, media area and intima/media ratio increased after 5 days and reached the maximum after 14 days. Whereas lumen area decreased with different time points. Antisense group, decoy group, antisense plus decoy group improved these observational index (P<0.05). The effect of antisense plus decoy group was more obvious than that of antisense group and decoy group alone. ICAM 1 and MCP 1 mRNA expression were examined after 6 hours of artery injury, but not evident after 1 days. They increased expression continuously after 3,5 and 7 days and decreased after 14 days. Comparing with model group, sense group and scramble group, antisense group, decoy group and antisense plus decoy group all lowered ICAM 1 and MCP 1 mRNA expression in every time point (P<0.05). Immunohistochemistry studies revealed ICAM 1 and MCP 1 protein were positive stain within six time points and maximal after 14 days. In antisense group, decoy group and antisense plus decoy group, ICAM 1 and MCP 1 protein synthesis decreased in every time point comparing with model group, sense group and scramble group. Western blot studies showed NF κB p65 was disperse positive stain after 6 hours of injury and increased after 1 day and reached the peak, but protein expression was weak after 14 days. Antisense group, decoy group and antisense plus decoy group treatment inhibited protein synthesis more significantly than those of model group, sense group

关 键 词：病理生理学 核因子кB对血管狭窄和新生内膜的作用 免疫组织化学检测 血管再狭窄 反义寡核苷酸 诱骗寡核苷酸 大鼠 

分 类 号：R363[医药卫生—病理学]