胎肝胰岛细胞联合移植治疗糖尿病大鼠

Combined transplantation of pancreatic islets and hepatocytes in the treatment of diabetic rats

目的 探讨胎肝胰岛细胞联合移植治疗糖尿病大鼠的效果 ,以及胎肝细胞移植诱导糖尿病受者鼠免疫耐受的可行性。方法 建立SD大鼠糖尿病模型 ,将实验动物随机分为正常对照组、糖尿病对照组、胰岛细胞组及肝细胞胰岛细胞联合移植组。将SD胎鼠的胰岛细胞移植于受者浆膜下 ,观察受者鼠的糖尿病病情变化及免疫状态。结果 移植后 5 8.8% ( 2 0 / 34)动物糖尿病得到缓解。联合移植组移植胰岛细胞存活期较胰岛细胞组明显延长 (P <0 .0 1) ;移植后 1周 ,联合移植组血清胰岛细胞肽水平明显高于胰岛细胞组和糖尿病对照组 (P <0 .0 1) ;脾细胞产生白细胞介素 2 (IL 2 )的活性联合移植组显著低于胰岛细胞组 (P <0 .0 0 1)。结论 胃浆膜下是大鼠胰岛移植较理想的移植部位 ;肝细胞移植可以明显延长移植胰岛细胞的功能存活期 ,并诱导受者产生特异性免疫耐受和非特异性免疫抑制。

Objective To study the effect of combined transplantation of pancreatic islets and hepatocytes on the treatment of diabetic rats and the possibility on hepatocytes inducing islet allograft tolerance. Methods Forty diabetic SD rats were randomly divided into 4 groups: normal control group,diabetic control group, pancreatic islet grafted group,and hepatocyte and pancreatic islet transplanted group. The pancreatic islets of fetal SD rats were implanted into the gastric subserosa of recipients. The alteration of diabetes and immune status were observed. Results There were 58.8% (20/34) diabetic rats cured after pancreatic islets transplantation. The survival time in the combined grafted group was longer than that in the pancreatic islet grafted group ( P< 0.01), and the serum C-peptide in the combined grafted group was higher than that in normal control and diabetic control group ( P<0.005). The activity of IL-2 production in was the combined grafted group inhibited obviously than that in the pancreatic islet grafted group( P< 0.001). Conclusions The gastric subserosa is a satisfactory site for grafting pancreatic islets. Hepatocyte grafting can prolong the survival time of transplanted pancreatic islets, and can induce the nonspecific immunosuppression and specific immunosuppression of recipient rats.