层流状态下高、低切应力对动脉重构及血管细胞粘附分子-1表达的影响

Effects of high and low shear stress on vascular remodeling and endothelial vascular cell adhesion molecular-1 expression in mouse abdominal aorta

目的制备小鼠腹主动脉狭窄模型,探讨近似层流状态下高、低切应力对动脉重构及VCAM-1表达的影响。方法 20只小鼠随机平均分为狭窄1 d组、7 d组、14 d组和假手术对照组,用动脉银夹建立腹主动脉局部狭窄模型,超声检测狭窄近心端和狭窄处血流动力学参数,计算切应力值;血管标本行HE染色和内皮血管细胞粘附分子-1(VCAM-1)免疫组织化学染色,定量分析动脉病理结构的改变及内皮VCAM-1表达的强度。结果狭窄动脉近心端和狭窄处分别形成低、高切应力血流区,与对照组比较,随着作用时间的增加,狭窄近心端动脉内中膜逐渐增厚、内皮VCAM-1表达逐渐增强,而狭窄处动脉无明显结构改变及内皮VCAM-1表达。结论血流动力学改变,尤其是低切应力可较早引起动脉重构,可能通过内皮VCAM-1的介导作用导致动脉粥样硬化的发生、发展,而高切应力则可能有抗动脉粥样硬化作用。

Objective To establish a mouse model of abdominal aorta stenosis and analyze the alterations in the arterial wall response to high and low shear stress.Methods Twenty mouse were randomized equally into 4 groups,including 3 test groups（1,7 and 14 day groups） with surgically induced stenosis of the abdominal aorta,and a sham-operated group without stenosis.The hemodynamics and the internal diameter of the blood vessel were measured by color Doppler flow imaging.The wall shear stress was calculated by Poiseiulle hydrodynamics formula（τm=η×4×Vm/D）.Pathological examination and immunohistochemistry were performed to observe the arterial morphological changes and the endothelial vascular cell adhesion molecule-1（VCAM-1） expression.The intimal-media thickness of the aorta was measured and endothelial VCAM-1 expression analyzed quantitatively.Results Regions of low and high flow shear stress were created upstream from the stenosis and within the stenosis,respectively.Compared with the sham-operated group,the mice with aorta stenosis showed gradually increased vascular intimal-media thickness and VCAM-1 expression intensity in the upstream aorta,but not within the regions of the stenosis.Conclusion Vascular remodeling may occur shortly after exposure to low shear stress,which plays a significant role in initiation and progression of the pathological process of atherosclerosis mediated by VCAM-1,whereas high shear stress may exert an anti-atherosclerotic effect.