摘要
目的:探讨静脉高压对大鼠上矢状窦的血流剪应力作用,以及载脂蛋白A-1结合蛋白(apoA-I binding protein, AIBP)介导的血管新生作用及潜在机制。方法:建立不同静脉压力梯度的大鼠模型(4组):A组大鼠行右侧颈动脉-颈外静脉吻合术+左侧横窦闭塞术+顶骨磨除术;B组大鼠行右侧颈动脉-颈外静脉吻合术+顶骨磨除术;C组大鼠行右侧颈动脉结扎术+右侧颈外静脉结扎术+顶骨磨除术;D组大鼠行顶骨磨除术。测量并计算3个月后上矢状窦剪应力。用Western印迹法、real-time PCR及免疫组化检测硬膜组织中AIBP、血管内皮生长因子(vascular endothelial growth factor, VEGF)的表达情况。将人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)分别于不同剪应力环境下培养后,检测细胞中AIBP、VEGF的表达及总胆固醇的含量。结果:静脉高压大鼠模型上矢状窦血流剪应力较D组明显增大( P < 0.05 ),且剪应力改变与静脉端压力正相关。real-time PCR和Western印迹显示,与D组相比,A组和B组大鼠硬脑膜中AIBP的表达下调、VEGF表达上调( P <0.01)。免疫组化结果示,AIBP在硬膜血管全层均有表达。体外实验中,HUVEC在高剪应力环境中与低剪应力环境下相比,AIBP表达量下调、VEGF表达上调、总胆固醇含量升高( P <0.05)。结论:静脉端压力升高可导致上矢状窦内血流剪应力增大,抑制AIBP的表达,减少细胞膜上胆固醇的流出,促进VEGF介导的血管新生。
Objective: To explore the effect of venous hypertension on blood flow shear stress in the superior sagittal sinus of rats, and the effect and underlying mechanism of apoA-I binding protein (AIBP) mediated angiogenesis. Methods: Four rat models with different venous hypertension gradient were established. Group A had right carotid artery and external jugular vein anastomosis, occlusion of left transverse sinus vein, and craniectomy of parietal bone. Group B had right carotid artery and external jugular vein anastomosis and craniectomy of parietal bone. Group C had ligation of right carotid artery and right external jugular vein and craniectomy of parietal bone. Group D had craniectomy of parietal bone. The shear stress of superior sagittal sinus was measured and calculated after 3 months. The expression of AIBP and vascular endothelial growth factor (VEGF) in dura tissue was detected using Western blotting, real-time PCR, and immunohistochemistry. Human umbilical vein endothelial cells (HUVECs) were cultured under different shear stress. After 24 h, the expressions of AIBP, VEGF, and total cholesterol in the HUVECs were analyzed. Results: The shear stress of superior sagittal sinus in the rats with venous hypertension was greater than that in the Group D ( P <0.05). The real-time PCR and Western blotting results showed that, compared to the Group D, the expression of AIBP decreased and VEGF increased in dura tissue of rats in Group A and B ( P <0.01). Immunohistochemical results showed that AIBP expressed in the whole vascular layer. In HUVECs, the AIBP decreased, whereas the VEGF and total cholesterol increased significantly in the high shear stress group than those in the low shear stress group ( P <0.05). Conclusions: Venous hypertension can increase shear stress in superior sagittal sinus. High shear stress may inhibit the expression of AIBP, reduce the cholesterol, and promote VEGF-mediated angiogenesis.
作者
李嘉楠
冯明陶
李强
许奕
张琪
刘建民
LI Jia-nan;FENG Ming-tao;LI Qiang;XU Yi;ZHANG Qi;LIU Jian-min(Department of Neurosurgery,Changhai Hospital,Navy Military Medical University,Shanghai 200433,China)
出处
《中国临床医学》
2019年第5期714-720,共7页
Chinese Journal of Clinical Medicine
基金
上海市科学技术委员会课题(17411971600)~~
