摘要
目的:研究血管损伤对新生内膜增生及核转录因子κb(NF-κb)、组织因子(TF)、内皮素-1(ET-1)、基质金属蛋白酶3(MMP-3)的影响。方法:对32只雄性新西兰大耳白兔进行穿刺股动脉,经导丝送入球囊,球囊扩张并拉伤腹主动脉建立血管损伤模型。损伤术后1 min经股动脉鞘管采血,4周后经心脏采血,处死兔子,分离损伤血管,进行固定、包埋,切片行苏木素伊红(HE)染色、碱性品红染色及NF-κb免疫组化染色后光镜下观察。切片经铅、铀染色后透射电镜下观察。使用计算机图像分析软件测量新生内膜厚度,分析确定血管壁损伤积分及NF-κb阳性细胞率,采用酶联免疫吸附法(ELISA)测定血清TF、ET-1和MMP-3含量,利用SPSS统计软件对血管损伤积分与血清TF、ET-1、MMP-3含量及NF-κb阳性细胞率进行相关性分析。结果:血管损伤积分与新生内膜厚度之间的最优拟合曲线是"S"形的三次曲线。NF-κb主要在新生内膜中表达,血管损伤积分与NF-κb阳性细胞百分率呈正相关,Pearson相关系数为0.916(P<0.05)。血管损伤积分与术后1 min TF,术后1 min及4周ET-1,术后1 min及4周MMP-3含量均呈正相关,Pearson相关系数分别为0.925、0.957、0.947、0.914和0.940(P均<0.05)。结论:血管损伤可以通过激活NF-κb途径,促进ET-1和MMP-3表达,从而促使新生内膜不断增生,导致血管负性重构。TF是血管损伤后导致新生内膜增生的始动因子。内弹力膜是反映血管损伤的关键结构,是阻碍新生内膜增生的唯一屏障。
Objective： To study the impact of vascular injury on neointimal hyperplasia and the expressions of nuclear transcription factor-κb（NF-κb）, tissue factor（TF）, endothelin-1（ET-1） and matrix metalloproteinase-3（MMP-3） in experimental rabbit model.Methods：A total of 32 male New Zealand big-eared white rabbits were used to establish vascular injury model by femoral artery puncture, balloon was sent to abdominal aorta via the wire followed by balloon dilatation to strain abdominal aorta. Blood sample was taken from femoral artery sheath 1 minute after operation, and the rabbits were killed at 4 weeks after operation, meanwhile blood sample was taken from the heart. Injured arteries were isolated, fixed and embedded; slices were stained by HE, basic fuchsine and NF-κb immunohistochemical methods for light microscope observation; slices were also stained by lead and uranium for transmission electron microscope observation. Neointimal thickness was measured by computer analysis, vascular injury integral and NF-κb positive cell rate were determined, blood levels of TF, ET-1 and MMP-3 wereexamined by ELISA. The relationship between vascular injury integral and the contents of TF, ET-1, MMP-3 and NF-κb positive cell rate were analyzed by SPSS statistical software.Results： The optimal fitting curve between vascular injury integral and neointimal thickness was S-shaped cubic curve. NF-κb was mainly expressed in neointima, vascular injury integral was positively related to NF-κb positive cell percentage, Pearson correlation coefficient was 0.916, P〈0.05. Vascular injury integral was positively related to the contents of 1 min post-operative TF; 1 min and 4 weeks post-operative ET-1; 1 min and 4 weeks post-operative MMP-3; Pearson correlation coefficients were 0.925, 0.957, 0.947, 0.914 and 0.940 respectively, all P〈0.05.Conclusion： Vascular injury may activate NF-κb pathway, promote ET-1 and MMP-3 expression, therefore accelerating neointimal hyperplasia, leading negative vascular remodeling,
出处
《中国循环杂志》
CSCD
北大核心
2016年第12期1210-1214,共5页
Chinese Circulation Journal
基金
宁夏自然科学基金(NZ14174)
关键词
血管损伤
新生内膜
增生
Vascular injury
Neointima
Hyperplasia
