颈动脉球囊损伤模型大鼠核转录因子κB变化与颈动脉血管内膜增生的关系

Correlation between nuclear factor-kappa B and vascular intimal hyperplasia in rat carotid artery after balloon catheter injury

目的:新生内膜异常增殖是血管成形术后再狭窄的主要原因,但其机制目前还不清楚。观察大鼠颈动脉球囊损伤术后核因子κB表达的变化及其与动脉内膜增生和血管重塑的关系。方法:实验于2007-01/05在深圳市人民医院动物实验中心完成。①实验材料:SPF级雄性SD大鼠36只,体质量350g左右。②实验方法:将大鼠一侧颈动脉行球囊损伤术作为实验组,另一侧颈动脉作为对照组,分别在颈总动脉球囊损伤后6h,3,7,14,28d后麻醉并处死大鼠,留取两侧颈总动脉标本。③实验评估:应用组织形态学方法检测内膜增生并进行计算机图像分析;同时通过凝胶电泳迁移率实验测定核因子κB的活性。结果:纳入大鼠36只,因造模失败和死亡排除6只,进入结果分析30只。①球囊损伤后,内膜面积在7,14,28d逐渐增厚,内膜/中层比率增长,与对照组比较,差异显著(P<0.05)。两组的中膜面积无明显变化。血管重塑指数在损伤后6h最大,之后不断减小。②核因子κB在对照组几乎不表达。而球囊损伤后6h即可见核因子κB表达,并于14d达高峰,28d仍有较强表达。实验组核因子κB各时间点与对照组比较差异均有显著性(P<0.05)。结论:大鼠颈动脉球囊损伤术后,核因子κB被迅速激活并持续增加,可能是内膜增生、血管重塑的重要机制之一。

AIM： Neointimal hyperplasia is the main reason for vascular restenosis after angioplasty. The mechanism is uncertain. This study explored nuclear factor- κB （NF- κB） expression changes after balloon catheter injury and its correlation with intimal hyperplasia of carotid artery and vascular remodeling. METHODS： The experiment was performed at Animal Experimental Center of Shenzhen People＇s Hospital from January to May 2007. ①Thirty-six male SPF SD rats weighing about 350 g were selected, and subjected to balloon catheter injury at one side carotid artery as experimental group and the other side as control group. All rats were executed under anesthesia on the 6^th hour, and 3^rd, 7^th, 14^th, and 28^th days after balloon injury, respectively to harvest common carotid artery samples. ②The intimal thickness and the expression of NF-κB were detected by HE-staining and gel electrophoretic mobility shift assay （EMSA） methods. RESULTS： Of the 36 rats, 6 were excluded due to failed modeling and death, and 30 rats were included in final analysis. ①The thickening of intima was observed on the 3^rd day after balloon injury, and became more significant on the 7^th, 14^th, and 28^th days. The area ratio of intima/media was increased significantly compared with control group （P 〈 0.05）. Vascular remodeling index reached the peak 6 hours after injury, and decreased thereafter. ②The expression of NF-κB was hardly observed in the control group. In injured rat carotid artery, NF-κB expression was firstly found 6 hours after injury, peaked on the 142 day, and remained high expression to the 282 day. There were significant differences at each point between experiment and control groups （P 〈 0.05）. CONCLUSION： After balloon catheter injury in rats, NF-κB is rapidly activated and enhanced gradually, which may be one of the important mechanisms for intimal hyperplasia and vascular remodeling.