课题背景：目前已知平滑肌细胞过度增殖是血管支架置入或血管成形后发生再狭窄的重要病因，但平滑肌细胞增殖的信号转导途径尚不完全清楚。认识平滑肌细胞增殖的信号转导途径对于阐明其发病机制具有重要意义。

应用要点：①本课题通过建立大鼠颈动脉内膜损伤模型，在以往实验的基础上进一步观察了大鼠颈动脉球囊损伤后新生内膜增殖发生再狭窄及局部核因子κB的表达变化。②结果提示损伤血管弹性回缩、新生内膜形成及负性重塑（慢性缩窄）是再狭窄发生的主要机制，核因子κB在球囊损伤后对血管平滑肌的增殖和迁移及再狭窄起着推动作用。

相关链接：平滑肌细胞迁移、增殖是新生内膜形成及再狭窄的关键因素，多种刺激因素均能诱导平滑肌细胞增殖，近年研究表明核转录因子κB的激活在平滑肌细胞增殖中起着至关重要的作用。

摘要
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350 g 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6 h，3，7，14，28 d 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7，14，28 d 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6 h 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6 h 即可见核因子κB表达，并于14 d 达高峰，28 d 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。
关键词：颈动脉球囊；核转录因子；血管内膜；增生；组织构建

姜昕，董少红，廖玉华，刘华东. 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[J].中国组织工程研究与临床康复，2008，12(7):1230-1234 [www.zglckf.com/zglckf/ejournal/upfiles/08-7/7k-1230(ps).pdf]

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

Abstract

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 6th hour, and 3rd, 7th, 14th, and 28th 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 3rd day after balloon injury, and became more significant on the 7th, 14th, and 28th 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 14th day, and remained high expression to the 28th 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.

Jiang X, Dong SH, Liao YH, Liu HD. Correlation between nuclear factor-kappa B and vascular intimal hyperplasia in rat carotid artery after balloon catheter injury.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(7):1230-1234(China) [www.zglckf.com/zglckf/ejournal/upfiles/08-7/7k-1230(ps).pdf]