低切应力对动脉重构与内皮黏附分子表达的动态变化

Dynamic effects of low shear stress on arterial remodeling and expression of endothelial cell adhesion molecules

目的探讨低切应力作用下不同时间点小鼠腹主动脉形态学重构及内皮黏附分子表达的变化。方法选择昆明小白鼠30只随机分为狭窄1、7、14、28 d组和假手术组,每组6只。用动脉银夹建立腹主动脉局部狭窄模型,彩色超声检测狭窄近心端血流动力学参数,计算切应力值;血管标本行HE染色和内皮P选择素及血管细胞黏附分子1(VCAM-1)免疫组织化学检测,分析动脉几何形态学改变和P选择素及VCAM-1的表达强度。结果与假手术组比较,狭窄1d组小鼠动脉壁开始增厚,内径缩小,壁厚内径比增大(P<0.05);与狭窄1d组比较,狭窄7、14和28 d组小鼠动脉内径明显缩小,壁厚与壁厚内径比进一步增大(P<0.01);各狭窄组P选择素明显上调(P<0.05),狭窄7、14和28 d组小鼠VCAM-1明显上调(P<0.05)。结论血流动力学改变可较早引起动脉血管重构,低切应力可能通过内皮炎症导致动脉粥样硬化的发生、发展。

Objective To investigate the changes of vascular structure and expression of adhesion molecules in endothelial cell at different time points under low shear stress. Methods Thirty mice were equally randomized into four test groups（stenosis for 1,7,14 and 28 clay groups） who underwent surgery of stenosis with an arterial silver clamp applied on abdominal aorta to create disfurbed flow, and one sham operation group without stenosis. The parameters of hemodynamics were measured by color Doppler flow imaging. The wall shear stress was calculated by Poiseiulle hydrodynamics formula. Pathological and immunohistoehemical examinations were performed to analyze the morphological changes and the expression of endothelial P-selectin and VCAM-1 in abdominal aorta. Results Low shear stress was demonstrated at upstream of stenosis. Compared with the sham group,with the increase in observation time,the changes of both wall thickness and the ratio of wall thickness to inner diameter were gradually increased at the area of low shear stress （P〈0.05）. The up-regulated expression of endothelial P selectin was seen from 1 to 28 days at the area of low shear stress,the peak was〈 0.05）,and the plateau was reached on clay 14. Conclusion Vascular remodeling can occur in a relatively short time after exposure to low shear stress. The low shear stress may play significant initial roles in the pathological process of atherosclerosis resulting from endothelial inflammation.