云南小耳猪胰岛细胞移植治疗糖尿病恒河猴免疫方案探讨

Immunosuppressive Treatment Protocol of Islets Xenotransplantation of Yunnan Miniature Pig into Diabetes Rhesus Monkey

目的探讨云南小耳猪胰岛细胞移植治疗糖尿病恒河猴的免疫抑制方案,观察其有效性及安全性.方法云南小耳猪胰岛细胞移植在糖尿病恒河猴肝内,移植后选择联合使用西罗莫司、他可莫司及吗替麦考酚酯的免疫抑制方案,监测移植前后胰岛素用量、血糖以及血清猪C肽水平和肝肾功能的变化,评价免疫方案对猪-猴异种胰岛细胞的保护作用.结果受体猴外源性胰岛素用量较术前明显减少(P<0.05);C肽水平较术前升高(P<0.05);无栓塞、感染、出血,肝肾功能无明显异常改变.结论联合使用西罗莫司、他可莫司及吗替麦考酚酯的方案可满足云南小耳猪-恒河猴异种胰岛细胞移植实验研究的需要,无明显副作用.

Objective The purpose of this study was to explore the immunosuppressive treatment protocol of islets xenotransplantation of Yunnan miniature pig into diabetes rhesus monkey,and observe the efficacy and safety.Methods The purified porcine islets were transplanted into the liver of diabetes rhesus monkey.Sirolimus,tacrolimus and mycophenolate mofetil were used as the immune suppression medications of post-transplant.The changes of insulin dosage,blood glucose levels,glycated hemoglobin,serum porcine C-peptide levels,liver function and kidney function were monitored before and after transplantation.Then the protection effect of immunization programs on the pig-monkey heterogeneous islet cell was evaluated.Results After operative,monkey exogenous insulin requirements decreased significantly （P ＜ 0.05）,while C peptide level was significantly higher than that before operation （P ＜ 0.05）.Embolism,infection and hemorrhage were not observed.The functions of liver and kidney were normal.Conclusion Joint use of sirolimus,tacrolimus and mycophenolate mofetil can meet the need of islet xenotransplantation of Yunnan miniature pig-rhesus monkey,without significant side effects.