A Study On Cytologic Mechanisms And Targeted Intervention Involving The Graft Arteriosclerosis In Rat Allogenic Orthotopic Abdominal Aortic Transplantation

Objectives Accelerated arteriosclerosis, the pathogenesis of which is poorly understood, remains a major problem in the long-term survival of transplant recipients, and there is no effective intervention so far. On the basis of our previous study, an intensive IRI (Ischemia Reperfusion Injury) rat allogenic orthotopic abdominal aortic transplantation model was used to investigate the rules of double-source repairing and the remodeling mechanism of SDF-l(Stromal cell derived factor-1) involved in this process. Methods Male Sprague-Darley rats received abdominal aorta grafts from male Wistar abdominal arteries and were randomly divided into three groups: prolonged cold ischemia group (PCI group, grafts preserved for 48 hours in 4℃ HC-A solution), control group (grafts preserved in 4℃ HC-A solution <1 hour) and SDF-1 antibody treated group (grafts preserved in 4℃ HC-A solution <1 hour, and 8μg/kg of SDF-1 antibody injected introperineally post-transplantation per day). Harvesting 5 grafts at 7 days, 14 days, 21 days, 28 days, 60 days and 90 days post operation, respectively. HE staining was carried out to detect the morphouses of graft aortae and the neointimalthickness was measured. Immunohistochemical staining was performed to detect the SDF-1/VEGF expression. Reverse-polymerase Chain Reaction (RT-PCR) demonstrated the expression of CXCR4, an only natraal biological receptor of SDF-1, and Vascular Endothelial Growth Factor (VEGF). Results No difference was found in comparison with the intima thicknesses between the control group and the PCI group in 14 days post-transplantation. The intima was thicker in the PCI group during the period of 14 to 60 days, but thinner than the control group after 60 days post-transplantation. The neointimal thickness of SDF-1 antibody treated group was unconspicuous, indicating SDF-1 plays a key role in recruiting stem cells to damaged intimae of abdominal aorta grafts for repairing and remodeling and SDF-1 antibody could slow down the endothelial chimerism by blocking this chemoattration. Furthermore, there was a significant relationship between the expression of SDF-1 and the thickness of the neointima of the grafts, while the relationship between the expression of VEGF and the thickness of the neointima was slim. The thickened portions of the neointima were most composed of Smooth muscle-like cells which derived from stem cells, and the media thickness changed little.Conclusions Prolonged cold ischemia could delay later grafts arteriosclerosis by earlier selectively chemoattrating stem cells to damaged intimae through SDF-1, which may be a pivotal signal molecule involved in the rat abdominal aortic grafts thicking process and an effective targeted intervention against which could slow down the intima incrassation rate.