Bio-Engineering Approach to Mechanisms of Angiogenesis Induced by Blood Flow

本实验采用兔耳腔技术，定量研究了在体微血管生成中血流和流动方向的壁面切应力的作用，以定量评价长期服用增加外周血流量的α_1受体阻断剂哌唑嗪对血管生成的影响。安装耳腔后，对家兔口服盐酸哌唑嗪（50 mg/l水溶液）。术后第4 ~ 23天，用活体视频显微镜观察并记录微循环的变化。量化腔室中血管化组织覆盖的相对面积（CA）、覆盖面积中的平均血管密度（MD）和相对血管面积（RA）。还估计了小静脉（20- 40 μ m ID）中的壁剪切应力。哌唑嗪处理的动物在POD 7-17的CA、POD 11-23的MD和POD 9-23的RA显著增加。治疗组的最终RA比对照组大约21%。哌唑嗪使血管壁剪切应力增加1.8倍，然后逐渐降低，直至13 POD达到对照水平。这些结果表明，慢性高流量负荷促进了体内血管生成过程中微血管结构的变化，表明微血管对壁剪切应力的适应性反应与大血管相同。这项研究已经通过实验证明，组织修复过程中的血管生成也受到血流产生的剪切应力的调节。

The effect of the blood flow and flow-oriented wall shear stress in microvascular angiogenesis was studied in vivo, by employing the rabbit ear chamber technique to quantitatively assess the effect on angiogenesis of chronic administration of the alpha_1 brocker, prazosin, which increases peripheral blood flow. Rabbits were treated with prazosin hydrochloride (50 mg/l in water) orally after ear chambers were installed. The microcirculation in the chamber was observed and recorded from 4 to 23 postoperative day (POD) by an intravital videomicroscope. The relative area covered by vascularized tissue in the chamber (CA), the mean vascular density in the covered area (MD) and the relative vascular area (RA) were quantified. Wall shear stress in venules (20-40mum ID) was also estimated. CA at 7-17 POD,MD at 11-23 POD and RA at 9-23 POD were significantly increased in the prazosin-treated animals. The final RA in the treated group was approximately 21% larger than that in the control group. The measured level of wall shear stress, which was increased 1.8 times by prazosin to at 9 POD,gradually decreased to ward the control level until they met at 13 POD.These findings suggest that the chronichigh flow load enhances microvascular structural change during angiogenesis in vivo, indicating the same adaptive responses of microvessels to wall shearstress as of large vessels. This study has experimentally proven that angiogenesis during tissue repair is also regulated by shear stress due to blood flow.