The Protective Effect Of Glucocorticoid-Free Immunosuppressive Regimen On Allogenic Islet Transplantation

Objective To evaluate the effect of anti-rejection of glucocorticoid-free immunosuppressive regimen on allogenic islet transplantation. Methods Islets of SD rats were isolated by ductal perfusion with collagenase and transplanted immediately by means of a transhepatic portal embolization in Wistar rats. The receptors were divided into three groups randomly. 0.3% carboxymethylcellulose(control group), tacrolimus(FK506)+ mycophenolate mofetil(MMF) and FK506+MMF +prednisone(Pred) were administered respectively for two weeks after operation. The concentrations of blood glucose were determinated developmentally in receptors with monitor and serum insulin andC-peptide were measured by radioimmunoassay. The change of body weight during the experimental period was observed. Moreover the sites of transplantation were observed morphologically. Results After isolated by digestion with collagenase, the yield of islets of SD rats was 634.17±148.05 islets per pancreas and the purity was 80% and the survival rate was beyond 90%. Compared with control group without immunosuppressive agents,FK506+MMF and FK506+MMF+Pred could lengthen the survival time of grafts significantly(P＜0.01) and the body weight of receptors increased in the two groups. There were many morphologically intact islets in liver of receptors two months after transplantation. Group FK506+MMF kept normal blood glucose, insulin and C-peptide beyond 60 days after transplantation, but compared with the former, group FK506+MMF+Pred secreted less C-peptide(P＜0.05) and maintained higher level of blood glucose concentrations(P＜0.01) after operation. The difference of insulin concentrations was no significant between the two groups. The level of blood glucose concentrations beyond the first two weeks after drug withdrawal in group FK506+MMF+Pred decreased obviously(P＜0.05), and the secretion of insulin and C-peptide increased, which were compared with the first two weeks after transplantation and the first two weeks after drug withdrawal.Conclusion 1. FK506+MMF and FK506+MMF+Pred both could provide effective immunosuppression. Glucocorticoid was detrimental to islets and the combined glucocorticoid-free immunosuppressive strategy of low-dose FK506 and MMF could protect islet grafts in islet transplantation without diabetogenic side effects. 2. High quality and more islet grafts could be got by twice digestion and non-purification. The method had better repetition.