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

采用2F - Forgaty导管（x3）损伤大白兔颈总动脉。损伤后28d，用直径2mm的ePTFE移植物代替内膜增厚的颈动脉。然而，增厚的内膜被夹持手术剥离，替换的移植物并不总是被发现是通畅的。除夹层外，假体与受损宿主动脉直径差异及内膜增厚是导致移植物闭塞的原因之一。因此，我们改变方案，在颈动脉损伤1或2周前对兔进行移植物置换。首先，我们研究损伤后1周和2周时间点ERK和PKB活性以及cyclin D1表达的差异，作为替代模型的Vor对照。损伤后1周和2周ERK和PKB活性与未损伤动脉基本相似。损伤后1周和2周cyclin D1表达高于未损伤动脉。结果表明，损伤后1周和2周增厚的内膜平滑肌细胞处于细胞生长周期。然后，我们研究了移植后1周和2周假体内膜SMC中ERK、PKB和cyclin D1的表达。与球囊损伤后2周相比，内膜的ERK和PKB没有明显的激活。与球囊损伤后2周相比，细胞周期素D1表达升高，但差异不显著。这些结果可能表明通过阻断ERK和PKB激活的信号通路来控制吻合口内膜增生的可能性。

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.