核转录因子NF-κB对大鼠血管球囊损伤后新生内膜形成的作用  

Role of Nuclear Factor kappa B in Neointima Formation after Balloon-Injured Rat Artery

作　　者：周俊[1] 陆国平[1] 吴春芳[1] 陈桢玥[1] 

机构地区：[1]上海交通大学医学院瑞金医院心内科,上海200025

出　　处：《上海交通大学学报（医学版）》2006年第8期869-872,共4页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市教委重点学科基金(8990207)资助项目

摘　　要：目的探讨核因子κBp65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后血管平滑肌细胞增殖和细胞基质金属蛋白酶的影响。方法建立SD大鼠颈动脉球囊损伤模型。随机分为7组,每组分为6个时相点(6h和1、3、5、7、14d),每个时相点3只大鼠。结果球囊损伤后7d,模型组、正义组、诱骗对照组血管内膜/中膜比达到高峰,较正常组、反义组、诱骗组、反义+诱骗组显著升高(P<0.05)。球囊损伤后第3天,免疫组化检测细胞增殖标记物BrdU的掺入,与模型组相比,反义组、诱骗组、反义+诱骗组BrdU标记指数明显降低(P<0.05)。Westernblot印迹法显示核因子κBp65蛋白表达在血管损伤后7d达高峰。大鼠颈动脉损伤后7d,基质金属蛋白酶(matrixmetalloproteinase-9,MMP-9)蛋白表达在反义组、诱骗组、反义+诱骗联合治疗组均较各自对照组降低。结论球囊损伤后血管平滑肌细胞增殖在不同时相点有动态变化;核因子κB反义和诱骗性寡核苷酸可抑制MMP-9的表达。Objective We examined the in vivo effect of the antisense or/and decoy oligonucleotide of nuclear fac- tor-kappa B （NF-kB） on balloon-injured smooth muscle cell proliferation and MMP-9 in the carotid artery of rats. Methods Sprague-Dawley rats underwent balloon-dilation injury of the left carotid artery. Rats were divided into 7 groups （n = 18） and each group included 6 time points （6 h and 1,3,5,7,14 d） （n = 3）. Results The mean intima/media ratio increased significantly in sense group,scramble group and model group and reached the maximum at 7 d after rat injured carotid artery, compared with normal group, antisense group, decoy group and decoy plus antisense group（P 〈0.05）. Immunohistochemistry studies revealed that compared with model group, BrdU labeling index in smooth muscles of carotid artery decreased obviously in antisense group, decoy group and decoy plus antisense group. Western blot studies showed that NF-kB p65 protein expression reached the peak at 7d after rat injured carotid artery. MMP-9 protein synthesis were maximal at 7d after rat injured carotid artery. MMP-9 protein expression in decoy group, antisense group and antisense plus decoy group decreased comparing with their corresponding control group. Conclusion Smooth muscle cell proliferation in vessel wall was dynamic ally changed after balloon angioplasty injury. Antisense and decoy oligonucleotide of NF-kB inhibited NFkB- activated MMP-9 expression.

关 键 词：核因子KB 新生内膜 反义寡核苷酸 诱骗寡核苷酸 

分 类 号：R363[医药卫生—病理学]