人工血管置换术是血管外科领域的重要手术方法，术后人工血管通畅率直接影响患者预后，人工血管新生内膜增生是移植物阻塞的主要原因，研究发现新生内膜增生与血管平滑肌细胞增殖密切相关。本项目组前期研究表明，放疗可抑制人工血管移植物新生内膜增生，而血管平滑肌细胞增殖的抑制可能是关键因素，但具体机制尚不明确。Skp2基因表达与血管平滑肌细胞增殖关系密切，并通过调控p27kip1影响细胞周期。综上提出假设：放疗可能通过抑制Skp2-DNA的复制，下调Skp2表达，进而作用于细胞周期中 G1/S期以抑制其增殖，并且减弱血管平滑肌细胞由吻合口向中央迁移和表型转换，最终抑制新生内膜增生的发生发展。本研究通过建立犬腹主动脉人工血管置换模型，从组织、细胞、分子水平研究放疗对Skp2/p27kip1通路负性调控作用，探究放疗影响人工血管移植物新生内膜增生的发生机制，以期寻找减缓人工血管新生内膜增生的关键放疗增敏因子。

Replacement of target vessel by prosthetic vascular graft is the most important surgical treatment for diseases involving major vessels and the patency rate of prosthetic grafts are crucial to survival of the patients. The most frequent cause of long-term grafting failure is neointimal hyperplasia(NIH). Previous studies demonstrated that perioperative radiotherapy could significantly reduce the intima thickness of the prosthetic grafts, and it can be proposed that radiotherapy inhibits NIH of prosthetic grafts through three pathways: 1)reduces cell migration from both proximal and distal anastomosis; 2)prevents cell recruitment, seeding, differentiation of circulating primary cells; 3)attenuates the cell infiltration and migration from perivascular tissue and neoadventitia via micropores of prosthetic grafts. Moreover, the proliferation, migration, phenotype transformation, apoptosis function of vascular smooth muscle cell plays the essential role in the entire process.Skp2 gene is considered highly associated with proliferation of VSMC and could affect the cell cycle via p27kip1 regulation. We hypothesize that radiotherapy could inhibit the duplication of Skp2-DNA and downregulate the expression of Skp2, in order to break the cell cycle in G1/S phase, as well as attenuate the VSMC migration from anastomosis to central area and phenotype transition. In the present study, we will investigate the effect of radiotherapy on NIH of prosthetic vascular grafts on canine aorta replacement model and explore the mechanisms by using morphological, immunological, cellular and molecular methods, essentially regarding the negative regulation of radiotherapy on Skp2/p27kip1 chaining pathway, in order to find a novel radioactive sensitizer in prevention of NIH of prosthetic vascular grafts.