Expression And Significance Of RANTES And CCR5in Cardiac Allograft Acute And Chronic Rejection

ObjectiveTo investigate the expression of regulated upon activation normal T-cell expressed and secreted(RANTES) and CCR5in cardiac allograft during acute and chronic rejection and the relationship between RANTES and CCR5with rejection.Materials and Methods1、Animal model and the group:Wistar rats are the donor,SD rats are the recipient. Three groups of rats were performed heterotopic cardiac transplantation using cuff-technique to construct the model of hear transplantation in the cervix of mice. A group (n=15):acute rejection group, Wistar to SD transplantation, there is nothing pretreatment with the donor and the recipient before transplantation; B group (n=20):Cyclosporine A, CsA group, Wistar to SD transplantation, there is also nothing pretreatment with the donor and the recipient before transplantation, but the recipients were treated with CsA monotherapy at10mg/kg by intraperitoneal injection every other day from the operation day, a total of8～10times. C group (n=25):Joint pretreatment using donor spleen cells and cyclophosphamide, Wistar to SD transplantation, the SD mice were pretreated with inoculation of donor spleen cells of Wistar mice at the number of5～10×10(?)7the first day followed by cyclophosphamide at50～80mg/kg IOCV the2nd day and transplanted the14th day.2、The Pathomorphology and immunohistochemistry:Heart explants and biopsies were dissected and fixed in different time(4d,7d,24d,56d)after operation according to the experimental requirements. The basal segments of explanted hearts were either stained with haematoxylin and eosin (H&E) or immunostained to detect the content of RANTES and CCR5using immunohistochemistry.Results1、The survival time of acute rejection group was (7.3±2.3)days; the survival time of CsA group was about (32.6±5.4) days; Joint pretreatment group, the heart could almost survive (209.7±42.8) days, and the cardiac arrest occurred only because of recipients death in most cases. There was significant difference in the survival time between the three groups (P<0.05)2、RANTES protein in brown color is expressed around vascular endothelial cells and medial smooth muscle cells in vessel wall of allograft heart, infiltrating mononuclear leukocytes in vessel wall and interstitialtissue of allograft heart; CCR5protein in brown color is expressed on the surfaces of infiltrating mononuclear leukocytes in vessel wall and interstitialtissue of allograft heart.3、The expression of RANTES and CCR5could be detected in the heart explants and biopsies at4,7,24and56days after transplant. In4,7days postoperation, A group had a stronger expression, the expression of B and C group was significantly weaker than A group. There was significant difference between them (P<0.05); In24days postoperation, B group had a stronger expression than C group and A group in4,7days (P<0.05); In56days postoperation, C group had a stronger expression than C group in24days (P<0.05)Conclusion1、The expression of RANTES and CCR5in cardiac allografts may plays an important role during the development of acute and chronic rejection.2、The expression of RANTES and CCR5in chronic cardiac allografts rejection is stronger than the expression in acute cardiac allografts rejection.