腹主动脉移植后小鼠外周血内皮祖细胞数量的动态变化及意义

Changes in the number of endothelial progenitor cells from peripheral blood and Significance in mouse abdominal aortic allografts

目的观察腹主动脉移植后小鼠移植物动脉硬化的病变过程及外周血内皮祖细胞（EPC）数量的动态变化，探讨EPC与动脉内膜损伤和修复的相互关系。方法以C57BL／6小鼠和Balb／c小鼠为供、受者，建立腹主动脉原位移植后移植性模型。术后3d、2周、4周、6周，观察移植动脉病理改变，并采用计算机图像分析系统分析移植血管内膜增生情况。使用流式细胞仪监测术后外周血中EPC数量的变化。结果术后3d，移植动脉内皮细胞损伤，并伴有明显的炎症细胞浸润。术后2周，即可观察到移植动脉新生内膜形成，存在急性排斥反应；术后4周、6周内膜厚度逐渐增生，移植动脉管腔明显狭窄。术后早期外周血中EPC的数量增多，3d时达到高峰，此后迅速减少，术后14和28d时，显著低于术前水平（P〈0．05）。结论通过同种小鼠腹主动脉原位移植可成功复制出移植物动脉硬化的病变特点；外周血中EPC的数量与移植动脉内膜损伤的修复密切相关，可能成为移植物动脉硬化的发病指标和干预靶点。

Objective To investigate changes in the number of endothelial progenitor cells （EPC） from peripheral blood and pathological feature in the development of transplant arteriosclerosis in mouse abdominal aortic allografts, and discuss their correlations. Methods A segment of abdominal aorta was transplanted orthotopically from C57BL/6 to Balb/c mice. The grafts were harvested at 3rd day, 2nd week, 4th week and 6th week after the operation and studied by light and electronic microscopy. Regional changes in the lumen and intima were measured with computer imaging analysis system. EPC from peripheral blood were quantified by flow cytometry. Results Endothelium injury and inflammatory cells infiltration were seen in the aortic allografts at 3rd day after transplantation. Neointimal lesions and acute rejection were observed as early as 2nd week after surgery. The lumen of allografts was significantly narrowed due to neointima hyperplasia and had progressed at 4th and 6th week postoperatively. The number of circulation EPC was increased from 1 st day after operation and reached the peak at 3rd day. Thereafter the number of EPC was decreased rapidly and significantly less at 14th and 28th day postoperation than that pre-operation. Conclusion Abdominal aortic transplantation from C57BL/6 to Balb/c mice presents typical pathological feature of transplant arteriosclerosis. The number of EPC from peripheral blood is related to the process of injured endothelial repair and neointima formation of aortic grafts. EPC count may be considered a novel biological marker and therapeutic intervention for transplant arteriosclerosis.