Study On The Correlation Between Adhesion Molecules And Chronic Rejection In Cardiac Allografts Of Rat

Background (Objective) : The main manifestation of chronic rejection of transplantation is allograft fibrosis and arteriosclerosis. The mechanism of chronic rejection remains elucidated, and there are currently no specific therapies to prevent or interrupt the process. Now, the specific index applied for the earlier diagnosis of chronic rejection becomes even more important. All of intercellular adhesion molecule-1 (ICAM-1), intercellular adhesion molecule-2(ICAM-2), vascular cell adhesion molecule-1(VCAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) are intensively relative to allograft rejection, but have not been identified with chronic rejection. In this study, the recipients were pretreated with specific donor spleen cells (SPC) and cyclophosphamide(CP) coadministration, and then the specific immune tolerance was induced to donor organs. By detecting the expression of ICAM-1, ICAM-2, VCAM-1 and PECAM-1, the relationship between adhesion molecules and chronic allograft rejection will be investigated in order to provide new theoretical basis for the treatment and prevention of chronic rejection.Method: Heterotopic cervical heart transplantation was performed, that is, the heart of Wister rats were transplanted into the cervical part of another SD rats. The rats were divided into following groups:non-treated group(acute rejection group, group A), Cyclosporin A(CsA)-treated group(immunosuppression group, group C) of heart allograft and recipient cyclophosphamide(CP) and donor splenocyte(SPC)-pretreated group. According to the time(T) of allograft harvest posttransplantation, CP and donor SPC-pretreated group was divided into two subset that Tsix-month group (immunotolerance group, group D). Nine heart allograft in each group. In different time after the operation the transplanted hearts were taken out in each group respectively. Immunohistochemical SABC method was used to detect the expression of ICAM-1, ICAM-2, VCAM-1 and PECAM-1.Result: (1) The survival time of cardiac allograft was significantly different in different groups in terms of the Kaplan-Meier existing curve. The survival mean time was (7.21±2.36) d in group A, (110.29±72.62)d in group C and more than 200d in group B and D. It was confirmed by Log-rank test that the survival time of the cardiac allografts in group D was longer than those in groups C (p<0.05) and the same result was seen in group B and A, which suggested that the recipient pretreated with SPC and CP should be more efficient than that with CsA, saying nothing of than non-pretreated group.(2) The expression level of ICAM-1, ICAM-2, VCAM-1 and PECAM-1 in cardiac allograft ICAM-1 manifested mainly in myocardial cytoplasm, myocardial interstitium and vessel wall at stained brown and yellow granules, and VCAM-1 expression were similar with ICAM-1. ICAM-2 was mainly observed in vascular endothelial cell of all groups, so was PECAM-1. Quantitative meassurement of ICAM-1, ICAM-2, VCAM-1 and PECAM-1 expression in the grafts was done through the method of integrity optical density under light microscope with computer analysis system. The tendency of their expression conformed to each other.The proteins of ICAM-1, ICAM-2,VCAM-1 and PECAM-1 were expressed at high level in group A and C, but at low level and in smaller erea in group B and D. There is no significant difference between group A and C or group B and D, P>0.05.But there is significant difference between group A and B or group A and D, P<0.05. The same result was also shown compared between group C and B or group C and D, P<0.05.Conclusion: (1) All of ICAM-1, ICAM-2, VCAM-1 and PECAM-1 have directcorrelations with the extent of myocardial fibrosis and arteriosclerosis in allografts.(2) The detection of ICAM-1, ICAM-2, VCAM-1 and PECAM-1 levels in cardiac allografts can reflect the extent of allograft fibrosis and arteriosclerosis, and provide the early diagnostic and preventive basis for chronic rejection. (3) It is fartherly approved that preconditioning with donor spleen cells followed by cyclophosphamid can induce the host immune tolerance to donor graft, so as to prolong the cardiac allograft survival time in rats.