The Role Of CXC Type Of Chemokines And Its Receptors In Acute Rejection After Liver Transplantation

Objective:To explore the dynamic changes of expression of chemokine Mig,IP-10,ITAC and their receptor CXCR3 around the time of acute rejection after liver transplantation.To explore the feasibility and possible mechanisms of the blocking of CXC chemokine receptor3(CXCR3) pathway by antisense peptide nucleic acid in prolonging liver allograft survival,to provide a new method and theory for clinical diagnosis and treatment for acute rejection after liver transplantation.Methods:Thirty cases of liver transplantation were observed,the changes of chemokines Mig,IP-10,ITAC in serum and CXCR3 expression in peripheral blood lymphocytes were measured 1 day prior to liver transplantation and 1,3,5,7days after liver transplantation,in AR group at diagnosis day and 3,7day after anti-rejection therapy;The models of orthotopic liver transplantation(OLT) and acute rejection of OLT were established by two-cuff technique.Rats were randomly divided into 4 groups:group of operation injury,group of OLT without acute rejection,OLT with acute rejection and OLT treated by FK506.The post-OLT survival time were recorded and pathological changes of grafts were evaluated by Banff's standard.The changes of expression of chemokines Mig,IP-10,ITAC and their receptor CXCR3 were measured 1 day prior to liver transplantation and 1,3,5,7day after liver transplantation;Rats were devided into 4 groups:group of OLT with acute rejection,group of OLT treated by FK506,OLT treated by asPNA and OLY treated by control asPNA.The post-OLT survival time were recorded and pathological changes of grafts were evaluated by Banff's standard.The changes of expression of chemokines Mig,IP-10,ITAC and their receptor CXCR3 were measured 1 day prior to liver transplantation and 1,3,5,7day after liver transplantation.Results:The expression of chemokines Mig,IP-10,ITAC and their receptor CXCR3 were ascended evidently from 3-5 days after OLT in clinical patients and rats of group of OLY with acute rejection.The post-OLT survival time of group treated by asPNA prolonged evidently,and the expression of chemokines Mig,IP-10,ITAC and CXCR3 were restrained evidently compared with controlled groups.Conclusions:The expression of chemokines Mig,IP-10,ITAC and their receptor CXCR3 ascended evidently before acute rejection occurring after OLT.This phenomenon is one part of reaction of acute rejection,it has alarm effect for acute rejection of OLT;The technology of asPNA can block the expression of CXCR3-mRNA,conducing to block or alleviate the reaction of acute rejection.