异基因小鼠颈动脉移植慢性排斥模型的制作

A murine model of chronic allograft carotid artery rejection

目的建立同种异基因小鼠慢性排斥反应的实验模型。方法运用显微外科血管吻合技术切取C57BL/6小鼠颈总动脉,原位行对端吻合植入C3H小鼠,建立同种异基因C57BL/6→C3H小鼠动脉移植慢性排斥模型,对照组为C3H→C3H同基因小鼠动脉移植,移植后不同时间(14d、30d、60d、120d)观察移植血管的动脉硬化情况以及受体小鼠脾脏细胞因子的表达水平。结果受体平均手术时间40min,手术成功率为100%。移植手术60天后,同种异基因移植组小鼠颈动脉移植段全部或大部分栓塞伴有明显的淋巴细胞浸润,对照组移植段血管通畅;异基因移植组脾脏组织中mIFN-γ和mIL-2表达明显上调,而对照组未见明显变化。结论通过显微外科法成功建立了同种异基因小鼠颈动脉移植慢性排斥反应模型,为探寻移植物慢性排斥机制提供有用的实验工具,其发生机制可能与Th1/Th2免疫偏离有关。

Purpose To establish the allograft murine model of carotid artery transplantation. Methods A segment of donor＇s carotid artery was harvested and end-to-end anastomosis was established between the donor and recipient carotid artery. The graft arteriosclerosis was observed at day 14, 30, 60 and 120 postoperatively. Lymphocytes infiltration in graft tissue and the expression of IFN-γ, IL-2 in spleen by RT-PCR were examined. Results Among 100 carotid artery transplants （allogeneic n = 50, syngeneic n = 50）, the mean time of recipient surgery was about 40 min, precluding the initial technical difficulties, the overall graft survival rate was 100%. Sixty days after transplantation, carotid artery grafts between syngeneic barriers did not develop any morphological aberrations, while the allogeneic grafts precipitated a self-limiting cellular infiltration and complete occlusion of the vessel. The expression of IFN-γ and IL-2 in the spleen in the allogeneic mice were significantly higher than that in the syngeneic groups. Conclusions This allograft murine model of arteriosclerosis extends the utility as a tool to study the molecular and cellular mechanisms rudiment to the evolvement of chronic rejection.