目的探讨动脉血流切应力变化对动脉壁形态结构、零应力状态以及血管平滑肌细胞(vascular smooth musclecells,VSMC)凋亡和去分化的影响。方法结扎大鼠左侧颈总动脉的部分分支,使血液全部经由枕动脉流出,造成左颈总动脉(LCA)低血流和低切应力以及对侧右颈总动脉(RCA)高血流和高切应力状态,以假手术不结扎动脉的动物为正常对照。取LCA和RCA,光镜和透射电镜观察血管壁组织形态学变化;测量血管零应力状态下的张开角;TUNNEL法进行原位细胞凋亡检测:免疫印迹法检测VSMC表型分化标志分子hl-calponin的表达。结果术后7d,低切应力LCA的内径减小了13%左右,壁厚内径比显著增加,张开角显著减小;内皮下层明显增厚,VSMC凋亡数量显著增加,VSMC表型分化标志分子hi—calponin的表达量显著降低。结论血流切应力显著降低会在短期内引起血管重建,提示VSMC凋亡和去分化可能是低血流和低切应力导致血管重建的早期事件之一。
Objective To reveal the morphological changes, zero-stress state, apoptosis and dedifferentiation of vascular smooth muscle cell ( VSMC ) of the arterial wall during vascular remodeling induced by alterations of flow shear stress. Methods The ligation on some distal branches of left carotid was done in the one and same rat to induce low shear stress state in the left common carotid artery (LCA) and high shear stress state in the right common carotid artery (RCA), while the rats with sham-operation without ligation were used as the normal control. The arterial morphology was examined by light microscopy and Transmission Electronic Microscope (TEM). Open angle was measured under the zero stress state. The apoptotic cells were detected by TdT-mediated dUTP-biotin nick end labeling (TUNNEL) staining. The expression of hl-calponin, which is a marker for the differentiated state of VSMC, was inspected with Western blotting. Results At the 7th day after operation of the LCA, the inner diameter was decreased about 13 %, the ratio of wall thickness to inner diameter was increased significantly and the open angle was reduced. Otherwise, the thickness of sub-endothelial and VSMC apoptotic were significantly increased while the hl-calponin decreased significantly. Conclusion The significantly decreased shear stress could induce the vascular remodeling in a short time. The apoptosis and dedifferentiation of VSMC might be one of early events during the vascular remodeling induced by low flow or low shear stress.