The Impact Of Rapamycin In Conjunct With CTAL4Ig And ICOSIg On Prevention Of Heart Allograft Rejection Of Mouse

The First PartEstablishment of heart transplantation on mouse earObjective: the purpose of the study is to reform a model of heart allograft rejection of mouse on ear for further research.Methods:transplant the heart of newborn C57BL/6 mouse within 24h to the ear subcutaneous of balb/c mouse,observe the survival rate of the allograft.Results:the suvival rate of homograft is 80% while the allograft is 63.6% in primary stage; when sophisticated, the survival rate of homograft can reach up to 98.1%.Conclusion:the reformed heart allograft model is reliable independent of microinstrument and easy to detect.The Second PartObjective:To study the impact of rapamycin in conjunct with CTLA4Ig on prevention of heart allograft rejection.Methods: Models of heart allograft transplantation on mouse ear was constructed and animals was divided into four groups in random.Group A: the control group with no treatment;Group B: intraperitoneal injection with CTLA4Ig 150ug/kg on day 0,2,4 after heart transplantation; Group C: intragastric administration with rapamycin 1mg/kg continuously for 14 days after transplantation; Group D: intraperitoneal injection with CTLA4Ig 150ug/kg on day 0,2,4 and intragastric administration with rapamycin 1mg/kg continuously for 14 days after transplantation.Observe the survial time of each group. Cardiac allograft biopsies after 8 days of transplantation was detected to evaluate the rejection. Results:minor dose of CTLA4Ig conjunct with rapamycin don't prolong the survial time significantly but allievate the infiltration of lyphocyte to allograft. Conclusion: CTLA4Ig conjunct with rapamycin showing synergy and may provide new ways to induce immune tolerance for further research.The Third PartObjective:To study the impact of rapamycin in conjunct with CTLA4Ig and ICOSIg on prevention of heart allograft rejection.Methods: Models of heart allograft transplantation on mouse ear was constructed and animals was divided into four groups in random.Group A: the control group with no treatment;Group B: intraperitoneal injection with CTLA4Ig 250ug/kg on day 0,2,4 and ICOSIg 100ug/d on day 1,3,5 after heart transplantation; Group C: intraperitoneal injection with rapamycin 0.5mg/kg continuously for 14 days after transplantation; Group D: intraperitoneal injection with CTLA4Ig 250ug/kg on day 0,2,4 and ICOSIg 100ug/d on day 1,3,5 after heart transplantation and intraperitoneal injection with rapamycin 0.5mg/kg continuously for 14 days after transplantation. Observe the survial time of each group. Cardiac allograft biopsies after 8 days of transplantation stained with HE and immunohistochemistry methods was detected to evaluate the rejection and heart allgraft apoptosis. Results:CTLA4Ig/ICOSIg conjunct with rapamycin prolong the cardiac allograft survial time significantly and allievate the infiltration of lyphocyte and apoptosis of myocardium. Conclusion: CTLA4Ig/ICOSIg conjunct with rapamycin showing synergy in prolonging the survial time and may improve the survial quality of allograft.