大鼠颈动脉球囊损伤后血管重构的超声特征及病理对照研究

Ultrasonic characteristics and histopathologic comparison of vascular remodeling after carotid balloon injury in rats

目的应用超声生物显微镜(UBM)技术探索大鼠颈动脉球囊损伤模型的血管重构特征,通过超声与病理特征对照,探讨UBM检测颈动脉损伤动物模型的应用价值。方法采用Fogarty(2F)球囊导管对22只10周龄SD大鼠(雄性、雌性各11只)建立颈动脉球囊损伤模型,左侧颈总动脉(common carotid artery,CCA)为损伤侧,右侧为对照侧。在损伤术前和术后7 d、14 d,对大鼠双侧CCA进行观察,UBM测量CCA内中膜厚度、内径、外径、管腔面积、血管面积,测量CCA收缩期峰值流速、舒张末期流速,计算血管阻力指数、剪切力等血流动力学参数。术后14 d处死动物取双侧CCA,横断面HE染色获取病理结构学数据。比较不同时间点大鼠颈动脉结构及血流动力学差异,比较损伤侧与对照侧动脉结构学差异。以Spearman相关分析与线性回归分析检验术后14 d超声与病理测值的相关性。结果①与术前相比,手术后14 d超声显示大鼠颈动脉内中膜厚度明显增加,内径变细,血管内剪切力增加(均P<0.05)。HE染色显示,雄性大鼠的内中膜厚度、新生内膜面积大于雌性大鼠(均P<0.001)。②大鼠颈动脉球囊损伤术后,管腔面积减小,但CCA均发生了代偿性的正性重构,血管面积增大。③大鼠CCA内中膜厚度、内径、外径、血管面积的超声测值与病理测值相关性良好(rs=0.819、0.965、0.896、0.955,均P<0.001),但血管面积的超声测值显著大于病理测值,差异有统计学意义(P=0.006)。结论UBM成像能清晰显示雄性与雌性大鼠CCA,并准确测量血管结构学数据,与病理相关性好;同时可测量血管血流动力学参数,为动脉损伤后血管重构的研究奠定了方法学基础。

Objective To detect the characteristics of vascular remodeling after carotid balloon injury model in rats using ultrasound biomicroscopy(UBM),and to discuss the application value of UBM technique by comparing ultrasonic characteristics with histopathological results.Methods Carotid balloon injury was performed in 10-week-old SD rats(11 female and 11 male)by 2F Fogarty balloon catheter.The left common carotid artery(CCA)was injured and the right side in the same animal was used as an uninjured control.Arterial structures and hemodynamics were evaluated pre-procedure and post-procedure at 7,14 days.The intima-media thickness(IMT)inner diameter,outer diameter,lumen area,vessel area,peak systolic velocity,end diastolic velocity of CCA were measured by UBM,and the vascular resistance index,shear stress and blood flow were calculated to evaluate the vascular hemodynamics.The histological data were obtained by H&E staining in cross-sections at 14 days after balloon injury.The characteristics of arterial structure and hemodynamic changes at various time points were compared,the structural changes of CCA between injured and control side after injury were compared.The Spearman correlation and linear regression were used to test the correlation between ultrasonic and histological measurements 14 days after balloon injury.Results ①Compared with pre-procedure,the IMT at 14 days after balloon injury was increased,the inner diameter was decreased,the shear stress in ultrasound was increased(all P<0.05).H&E staining histological test showed that IMT and neointima area in male rats were larger than those of female rats(all P<0.001).②After carotid balloon injury,the lumen area decreased,but the CCA underwent compensatory positive remodeling and the vessel area increased.③Significant correlations were demonstrated between UBM and histology in IMT,inner diameter,outer diameter and vessel area of CCA(rs=0.819,0.965,0.896,0.955;all P<0.001).The vessel area value measured by UBM was larger than that of histology(P=0.006).Conclusions The CCA of rats can be showed clearly by UBM in males and females.The arterial structure cab be measured by UBM accurately with good correlation with histology,as did arterial hemodynamic parameters,which may be benefit for the study in carotid balloon injury model of rats.