Effects of cyclosporine combined with transforming growth factor beta 1 plasmid on rat immunological reaction following liver transplantation / 中国组织工程研究

ABSTRACT

BACKGROUND: Most patients who underwent liver transplantation would suffer acute rejection or transplanted liver failure resulted by chronic rejection, therefore, inducing specific immune tolerance via varied pathways is the ideal method to solve this problem. OBJECTIVE: To treat rat transplanted liver by injecting transforming growth factor β1 (TGF-β_1) plasmid, and to analyze the relationship between TGF-β1 and allograft rejection from gene level. METHODS: A total of 30 male, Wistar rats were served as allogenic liver donors, and 10 male, SD rats served as syngeneic donors Totally 40 male SD rats were served as liver recipients, and divided into 4 groups by order number table ailogenic transplantation, syngeneic transplantation, ciclosporin, and ciclosporin plus TGF--β_1 groups. In each group, rat orthotopic liver transplantation model was established by modified Kamada and improved two-cuff technique. After modeling, rats were received cyclosporine 1-5 days in the cyclosporine group, or intraperitoneal injected ciclosporin for 1-5 days, combined with TGF-β_1 plasmid 0-2 days in the cyclosporine plus TGF-β_1 group. No intervention was performed in the other groups. The survival time of rats were recorded, and the pathological changes was detected at days 3, 7, 14, 21, and 28 after transplantation, then the mixed lymphocyte culture was performed. RESULTS AND CONCLUSION: The survival time of rats in syngeneic transplantation group and cyclosporine plus TGF-1,β_1 group was more than 60 days, which was obviously greater than that of allogenic transplantation and cyclosporine groups (P< 0.05). The histopathologic slide showed that there was moderate and severe acute rejection, with evident intrahepatic inflammatory cell infiltration in the allogenic transplantation and cyclosporine groups. Few rejections were observed in the syngeneic transplantatior group, which was close to the normal lever tissues. Mixed lymphocyte culture of the cyclosporine plus TGF-β_1 group was superior to the syngeneic transplantation group or cyclosporine group (P < 0.05). The results demonstrated that cyclosporine combined with local injection of TGF-β_1 plasmid can relieve post-transplant immune rejection.