免疫隔离大鼠胰岛移植治疗小鼠药物性糖尿病的研究

Xenotransplantation of Immunoisolated Rat Islets for Treatment of Drug-induced Diabetic Mice

目的 探讨免疫隔离的胰岛异种移植治疗小鼠药物性糖尿病的可行性。方法 新生 Wistar大鼠胰岛分离后包裹在由 THF制成的免疫隔离室内 ,移植给药物诱导的 Balb/ c糖尿病小鼠。移植后不使用免疫抑制剂 ,观察血糖变化情况。结果 免疫隔离及非隔离的胰岛均显示了良好的对葡萄糖加茶碱刺激的反应能力 ,胰岛素的释放量在 2组间无明显差异。移植后免疫隔离胰岛移植组血糖在 3d内降至正常 ,平均维持正常血糖 (72 .8± 3.1) d,多饮、多尿现象明显改善。单纯胰岛移植组血糖降低后仅维持平均 (8.1± 0 .5 ) d。对照组小鼠则持续高血糖状态。组织学检查示免疫隔离室外形成厚度不一的纤维化反应层 ,隔离室内大部分胰岛坏死 ,部分可见残存的胰岛。结论 免疫隔离胰岛异种移植能有效延长移植物的存活 ;

Objective To investigate the feasibility of xenotransplantation of immunoisolated islets treating diabetes mellitus. Methods Islets were isolated from neonatal Wistar rats and encapsulated in Thomapor hollow fiber. After glucose stimulated insulin secretion test, the encapsulated and unencapsulated islets were intraperitoneally transplanted into streptozotozin induced diabetic Balb/c mice. No immunosuppressive therapy was used. Results The immunoisolated and non isolated islets were responsive to glucose and isobutylmethylxanthine stimulation. There was no significant difference in insulin secretion. After transplantation, the fasting plasma glucose levels in immunoisolation group were reduced to normal range within 3 days and maintained a mean normoglycemia for (72 8±3 1) days; the diabetic symptoms were ameliorated. While in the non isolatation group normoglycemia was maintained only for (8 1±0 5) days and the mice in the control group still showed diabetic condition. Histologic examination showed a fibrotic reaction to immunoisolation device and the most of islets encapsulated in THF were not survived. Conclusion Xenotransplantation of immunoisolated islets can effectively prolong xenograft survival time without immunosuppression; The fibrotic overgrowth around immunoisolation device is the main reason for graft failure.