白细胞介素-8对兔腹主动脉狭窄和平滑肌细胞增殖的影响  

Interleukin-8 monoclonal antibody attenuates smooth muscle cell proliferation and balloon inflation-induced abdominal aorta stenosis in rabbits

作　　者：孟存良[1] 齐晓勇[1] 李英肖[1] 党懿[1] 刘惠良[1] 王天红[1] 袁华兵[1] 倪艳辉[1] 刘光[1] 武振朝[1] 郜利会[1] 

机构地区：[1]河北省人民医院心脏中心,石家庄05005l

出　　处：《中华心血管病杂志》2012年第12期1056-1061,共6页Chinese Journal of Cardiology

基　　金：河北省自然科学基金项目（200700095）

摘　　要：目的观察球囊损伤腹主动脉后白细胞介素-8（IL-8）水平变化对兔腹主动脉狭窄和平滑肌细胞增殖的影响。方法新西兰大白兔36只，随机分为实验组、IL-8单克隆抗体治疗组（治疗组）、对照组，每组12只。实验组和治疗组动物穿刺股动脉，送人球囊拉伤腹主动脉。治疗组动物通过耳缘静脉注射IL．8单克隆抗体进行干预。对照组动物只进行股动脉穿刺和留置鞘管，不进行球囊扩张拉伤腹主动脉。分别于实验前和实验后4h、1d、3d、1周、2周、4周取外周静脉血4ml，检测血清IL-8水平。4周后处死动物，取腹主动脉进行病理组织学检查，应用光学显微镜和计算机病理图像分析系统分析测定以下指标：内膜中膜厚度、面积，计算血管狭窄程度。增殖细胞核抗原（PCNA）染色分析后，测定每40倍视野中PCNA阳性细胞，计算阳性细胞数和阳性细胞百分率。结果实验组动物球囊损伤4h后血清IL-8水平即开始升高，术后1d达到峰值，持续增高4周，且均明显高于治疗组和对照组（P均〈0．01）。治疗组和对照组动物IL-8水平无上述变化规律。实验组PCNA阳性细胞比例明显高于治疗组与对照组（P均〈0．05），治疗组明显高于对照组（P〈0．05）。相关分析显示IL-8水平与PCNA阳性细胞数呈正相关，相关系数r=0．864（P〈0．01）。实验组动物腹主动脉明显狭窄，组织学检查内膜面积和中膜面积、血管狭窄程度等指标大于治疗组和对照组（P均〈0．01），治疗组管腔有所狭窄，对照组动物管腔无明显变化，治疗组与对照组比较差异无统计学意义。相关分析显示，IL-8水平与PNCA阳性细胞数、内膜厚度、内膜面积、中膜厚度、中膜面积等呈正相关（相关系数r分别为0．684，0．894，0．783，0．801，0．912，P均〈0．01）。结论球囊损伤引起IL-8水平高表达，导致腹主动脉平滑肌细胞增殖�Objective To observe the effects of interleukin-8 monoelonal antibody on smooth muscle cell proliferation and balloon inflation-induced abdominal aorta stenosis in rabbits. Methods Thirty- six New Zealand white rabbits were randomly assigned to balloon inflation group （group A, n = 12）, interleukin-8 monoclonal antibody pre-treated rabbits （2 mg/kg for 3 days before balloon inflation, group B, n = 12 ） and sham-operated control group （group C, n = 12 ）. Peripheral blood was collected before experiment and at 4 h, 1, 3, 7, 14, and 28 days post balloon inflation or sham operation and the levels of IL-8 were measured by enzyme linked immunosorbent assay （ELISA）. The ratio of positive and negative masculine cells in the high power microscopic field was determined in proliferating cell nuclear antigen （PCNA） stained slide. Histopathologie examination was performed in abdominal aorta and luminal area, intima and tunica media area were measured. Results Plasma interleukin-8 began to rise at 4 h and peaked at 1 day and remained increased up to 28 days after balloon inflation in rabbits of group A, plasmainterleukin-8 level in group A was significantly higher than in group B and C at 4 h and thereafter post operation. The ratio of positive and negative masculine cells was significantly increased in group A compared to group C and was significantly lower in group B than in group A. Abdominal aorta stenosis, luminal area, intima and tunica media area were significantly reduced in group B than in group A. Correlation analysis indicated that there were positive relations between plasma IL-8 level and intima thickness, area of intima and tuniea medias, respectively （ r = O. 894,0. 783,0. 801,0. 912, all P 〈 0. 01 ）. Conclusions Plasma IL-8 level is increased in this abdominal aorta stenosis model and is positively correlated to the severity of abdominal aorta stenosis. IL-8 monoclonal antibody could significantly reduce abdominal aorta stenosis in this abdominal aorta stenosis model.

关 键 词：主动脉 腹 肌细胞 平滑肌 细胞增殖 白细胞介素8 

分 类 号：R543[医药卫生—心血管疾病]