Significantly Prevent Acute Rejection In Liver Transplantation Via Ex Vivo Perfusion With Isotope Marked Anti-class II Antibody.

Background and Aim:Acute rejection is the tough problem to medicine science constantly from begining of organ transplantation.The best way to prevent or treat is to use immunodepressant after transplantation,which has some disadvantages just like lifetime administration,low immunological function,augmented occasion for infection or tumor and expensive cost.Besides,other methods including microencapsulated transplantation of cells or tissue,donor cell infusion before transplantation and using various kinds of antibodies have no conspicuous effect in clinic.It is the key for the study to find a new way to degrade the acute rejection happeing and limit the dose and time of using immunodepressant at some time.This study combine biological ans atomical way together,establish a graft liver ex vivo perfusion model of swine liver transplantation,observe the effect of isotope marked anti-classâ…¡antibody to the earlier acute rejection after liver transplantation,explore the mechanism of action and provide theoretical and experimental prove to clinic application.Methods:Swine are divided into three groups at random for orthotopic liver transplantation:graft livers are treated respectively with NS,2E9/13F(ab')₂ and isotope marked 2E9/13F(ab')₂ via ex vivo perfusion,metered items including live time,liver function,serum cytokines and histopathologic examination.Establish mixed lymphocyte culture model,observe the lymphocyte proliferation and activation,determine the mRNA of relative cytokines,compare the difference between in and ex vivo environment and analyze the reason.Results:The live time of third group are higher than the second and first group obviously(survival rate of two weeks respectively were100%,83.3%,50%;survival rate of one month respectively were 66.7%,50%,0%;survival rate of two monthes respectively were 50%,16.7%,0%).The serum total bilirubin of first group(7.87±1.10 vs 4.88±0.56 vs 4.41±0.76 mg/dl;p＜0.05),ALT(58±7.58 vs 41.25±4.06 vs 38.25±8.46 IU/L;p＜0.05),AST(1499.75±437.50 vs 675±432.14 vs 825.5±344.04 IU/L;p＜0.05)on day 7th after transplantation are higher than the second and third group.However,the indexes on day 13th an 14th of the second group are higher than the third group remarkably,including total bilirubin(4.00±0.24 vs 1.92±0.75,4.26±0.58 vs 1.82±0.65 mg/dl;P＜0.05),AST(600.75±164.16 vs 243.5±162.32,718±273.54 vs 223±147.67 IU/L;P＜0.05)and ALT(40.75±3.18 vs 28.75±5.22,42.5±4.53 vs 30.25±3.49 IU/L;P＜0.05).The average value of IL-2(462.55±117.39 vs 70.3±14.57vs 88.7±18.67 pg/ml;P＜0.05)on day 4th in first group are higher than homeochronous average value of the second group and the third group.And the average value of IFN-r(2479.85±573.62 vs1759.2±255.55 vs139.56±46.37 pg/ml;P＜0.05),IL-10(1975.00±511.67 vs 2143.25±507.49 vs750.27±199.44 pg/ml;P＜0.05),TNF-a(107.15±29.74 vs 85.04±10.35 vs7.40±2.04 ng/ml;P＜0.05)on day 6th in first and second group are also higher than homeochronous average value of the third group.It is proved that growth rate of lymphocyte,mRNA level of IL-2,IFN-r,TNF-a in third group are less than which in first and second group based on ex vivo experiments,and there is no difference among three groups about the level of IL-10 mRNA.Conclusions:Isotope 188Re marked anti-classâ…¡antibody could Significantly prevent acute rejection in liver transplantation via ex vivo perfusion,prolong the live time of graft liver and no persistent or conspicuous side effect.188Re marked anti-classâ…¡antibody could be used in clinic conveniently as ancillary drug for non-specificity immune treat,lead -ing to reduce the dose and time of immunodepressant effectively.