胱抑素C在兔血管成形术后再狭窄中对血管外膜的影响

Effect of cystatin C on adventitia of restenosis in rabbits after angioplasty

目的探讨兔腹主动脉血管成形术后胱抑素C水平变化对兔腹主动脉再狭窄血管外膜的影响及机制。方法选择新西兰大白兔48只,随机分为损伤组、治疗组(胱抑素C单克隆抗体治疗)、对照组,每组16只。分别于术前和术后8h、1d、1周、3周、6周取外周静脉血,检测血清中胱抑素C水平。术后6周取腹主动脉行HE染色、血管形态计量分析和血管外膜细胞计数;同时行平滑肌肌动蛋白、增殖细胞核抗原(PCNA)免疫组织化学染色,计算PCNA增殖指数。以血管重构指数、外弹力板围绕面积(EELA)、内弹力板围绕面积(IEIA)变化评价血管重构情况,以剩余狭窄率、血管腔面积变化衡量血管狭窄情况。结果与对照组比较,损伤组血管腔面积、EELA、IELA明显增大,血管重构指数为0.871,剩余狭窄率为33.1%。治疗组胱抑素C水平较损伤组明显下降,血管腔面积、EELA、IELA缩小程度较损伤组明显减轻,血管重构指数为0.748,剩余狭窄率为19.7%(P<0.05)。相关分析显示,胱抑素C水平与血管腔面积、新生内膜面积、IELA、EELA及PCNA阳性细胞数呈正相关(P<0.01)。结论兔腹主动脉球囊损伤后血管外膜细胞被激活,发生增殖、表型转化,参与了血管重构及血管再狭窄发生。胱抑素C水平高表达是发生腹主动脉狭窄的独立危险因素。

Objective To study the effect of cystatin C on adventitia of abdominal aorta restenosis in rabbits after angioplasty and its mechanism.Methods Forty-eight New Zealand white rabbits were randomly divided into injury group,cystatin C monoclonal antibody treatment group and control group （16 in each group）.Their serum cystatin C level was measured before and 8 h,1 day,and 1,3,6 weeks after operation.The morphology of abdominal aorta was analyzed by morphometry with HE staining and the number of adventitial cells was ccalculated 6 weeks after operation.Smooth muscle actin and PCNA expression were detected with immunohistochemical staining.Proliferation index of PCNA was calculated.Vascular remodeling was assessed according to the VRI,EELA and IEIA.Vascular stenosis was assessed according to the residual stenosis and vascular cavity area.Results The vascular cavity area,EELA and IELA were significantly larger in injury group than in control group with a vascular remodeling index of 0.871 and a residual stenosis rate of 33.1％.The serum cystatin C level was significantly lower and the vascular cavity area,EELA,IELA were significantly smaller in treatment group than in injury group with a vascular remodeling index of 0.748 and a residual stenosis rate of 19.7％ （P＜0.05）.Correlation analysis showed that the serum cystatin C level was positively related with the vascular cavity area,neointima area,IELA,EELA and PCNA-positive cells （P＜ 0.01）.Conclusion The adventitial cells are activated and proliferated in abdominal aorta of rabbits after injury with their phenotype transformed,thus participating in vascular remodeling and restenosis.Overexpression of cystatin C is an independent risk factor for the stenosis of abdominal aorta.