Signal pathway in anastomotic intimal hyperplasia : to establish the strategy for anastomis intimal hyperplasia after bypass grafting with small diameter prosthesis

通过2F Forgaty导管（× 3）损伤白色家兔的颈总动脉。伤后28天取颈总动脉，用直径为2mm的ePTFE人工血管替代内膜增厚的损伤动脉。然而，通过夹闭手术将增厚的内膜剥离，置换的移植物并不总是通畅的。除夹层外，人工血管与损伤的宿主动脉之间的直径差异和内膜增厚也是导致移植物闭塞的原因之一。因此，我们改变了实验方案，对颈动脉损伤前1或2周的家兔进行了移植物置换。首先，我们以Vor为对照，在替代模型中研究了损伤后1周和2周ERK和PKB活性以及cyclin D1表达的差异。ERK和PKB活性在伤后1周和2周与未伤动脉基本相似。而损伤后1周和2周cyclin D1的表达明显高于未损伤动脉。结果表明，损伤后1周和2周增厚内膜中的平滑肌细胞处于生长周期中。然后，我们研究了ERK，PKB和cyclin D1在移植物置换术后1周和2周的时间点的人工血管内膜SMC中的表达。与球囊损伤后2周相比，内膜ERK和PKB无明显激活。cycline D1表达较球囊损伤后2周有所增加，但无统计学意义。这些结果提示，阻断ERK和PKB信号通路可能是控制吻合口内膜增生的重要途径。

The common carotid artery of white rabbits was injured by the passage of 2F Forgaty catheter (x3). The injured carotid artery with thickened intima was replaced with ePTFE graft with 2mm diameter 28days after injury. However, the thickened intima was dissected by clamping procedures and the replaced grafts were riot always found to be patent. In addition to the dissection, diameter difference between the prosthesis and the injured host artery with thickened intima was one of the reasons of occlusion of the replaced grafts. Therefore, we changed the protocol, and the graft replacement was performed in the rabbits of which carotid artery was injured 1 or 2 weeks before. At first, we studied the differences of ERK and PKB activity and the expression of cyclin D1 at the time point 1 and 2 weeks after injury as the Vor control in the replacement model. The activities of ERK and PKB at the time point 1 and 2 weeks after injury was amost similar to that of uninjured artery. However, cyclin D1 expression was higher 1 and 2 weeks after injury than that of uninjured artery. These showed that smooth muscle cells in thickened intima 1 and 2 weeks after injury were in the cell cycle of growth. And then, we studied the ERK, PKB, and cyclin D1 expression in the intima SMC of prosthesis at the time point of 1 and 2 weeks after graft replacement. ERK and PKB of intima were not impressively activated compared to those of 2 weeks after balloon injury. And cycline D1 expression was higher, but not significant, than that of 2 weeks after balloon injury. These results may show the possibilities that the anastomotic intimal hyperplasia could be controlled by blocking the signal pathway via ERK and PKB activitivation.