Research On Prevention Of Sodium Ferulate And Ciclosporin A On Allograft Angiopathy In Rats

Objective:To investigate the prophylactic effect of ciclosporin A used only and combined with sodium ferulate on allograft angiopathy in rats,then discuss their potential mechanism of action.Method:The model of allogeneil graft of carotid artery was set up. According to the administration of drugs after transplantation, 45 rats were divided into three groups: A groups as control group, no intervention; B group, ciclosporin A used only;C group, ciclosporin A combined with sodium ferulate. Blood serum samples were taken before operation and the 1st , 4th and 8th week after transplantation, respectively. Blood lipid, MDA, ET, NO and the activity of SOD were detected. The thickness of the intimal layer was observed by light microscopy and the expression of TNF-α,TGFβ1,ICAM-1,VCAM-1and NF-κB were detected by immunohistochemistry in allograft.Result:The thickening degree of the intimal layer of allograft was lessened in combined with sodium ferulate more than ciclosporin A used only. Sodium ferulate decreased triglyceride in blood serum; Sodium ferulate decreased ET-1 and increased NO by rivalrying endothelin receptor directly; Sodium ferulate enhanced the activity of SOD and decreased the synthesis of MDA; Sodium ferulate inhibited the expression of TNF-α,TGFβ1,ICAM-1,VCAM-1and NF-κB. The level of ET and MDA in cyclosporine A-treated group were higher than in control. However, the change of the SOD activity is opposite. ET and MDA decreased while NO and the SOD activity increased in combination-treated group. Furthermore, the expression of ICAM-1,VCAM-1and NF-κB was the lowest in the three groups.Conclusion:The treatment of Ciclosporin A combined with sodium ferulate in vasotransplantation is able to delay the development of allograft vasculopat. The effects of sodium ferulate possibly includes in decreasing TG; increasing the synthesis and release of NO by rivalrying ET receptors; elevating the SOD activity to clean up free radical, depress MDA and prevent the injury of lipid peroxidation; resisting inflammatory. Many pathways including inhibiting the activation and generation of T lymphocyte and reducing reject reaction were involved in the protection of vascular endothelial cell to prevent allograft vasculopat vascular sclerosis.