霉酚酸、雷帕霉素及FTY720在体外对成人胰岛功能的影响  

Effects of MPA, sirolimus, FTY720 on human pancreatic islet function in vitro

作　　者：陈向锋[1] 刘志宏[1] 董维平[1] 王煜非[1] 王鉴波[1] 李永翔[1] 谭建明[1] 

机构地区：[1]上海市第一人民医院移植泌尿科上海市器官移植临床医学中心,200080

出　　处：《中华器官移植杂志》2005年第5期307-309,共3页Chinese Journal of Organ Transplantation

基　　金：上海市社会发展基金项目(沪卫科教[2002]53号);福建省科委重大课题(2002Y007);全军"十五"重大课题(04Z007)

摘　　要：目的探讨霉酚酸、雷帕霉素及FTY720对体外培养的成人胰岛功能的影响。方法将分离、纯化后获得的成人胰岛细胞分别与不同浓度的霉酚酸、雷帕霉素和FTY720混合培养24h,然后测定经各药物作用后的胰岛细胞在低糖(2.8mmol/L)和高糖(16.7mmol/L)刺激下胰岛素的释放量,并计算刺激指数。结果对照组(未添加药物)的胰岛细胞在低糖和高糖刺激下胰岛素的释放量分别为(7.37±1.74)ng/ml和(15.15±5.39)ng/ml,刺激指数为2.06±0.46。与对照组相比,添加霉酚酸的胰岛细胞在低糖和高糖刺激下胰岛素的释放量均明显下降(P<0.01),刺激指数亦明显下降(P<0.05);添加雷帕霉素组,低糖和高糖刺激时胰岛素的释放量均有下降(P<0.05),但刺激指数仅在雷帕霉素浓度为1.0ng/ml时明显下降(P<0.05);添加FTY720组,低糖刺激时胰岛素的释放量明显低于对照组(P<0.05),高糖刺激时,胰岛素释放量仅在FTY720高浓度组有明显下降(P<0.05),刺激指数也有明显下降。结论相对来说,在体外雷帕霉素和FTY720对成人胰岛细胞的毒性作用较小;胰岛移植后,选择免疫抑制方案应遵循低剂量原则。Objective To observe the effect of three immunosuppressive agents on the function of human adult islets of langerhans in vitro, and explore the suitable immunosuppressive protocols for human islet transplantation.Methods In vitro, the isolated and purified islets were incubated with the immunosuppressive agents (mycophenolic acid, sirolimus, and FTY720) at different concentrations for 24 h, then stimulated by glucose at low ((2.8) mmol/L) and high ((16.7) mmol/L) levels. The (insulin) release after stimulations was detected using ELISA kit, and stimulation index was calculated.(Results) In control group (no agents exposure), the insulin release were ((7.37)±(1.74)) ng/ml at low (level) and ((15.15)±(5.39)) ng/ml at high level respectively, with stimulation index achieved to (2.06)±(0.46). Compared to control group, treatment with mycophenolic acid led to dramatic reduction of (insulin) release (P<(0.01)) and stimulation index (P<(0.05)); treatment with sirolimus also induced the (decrease) of insulin release (P<(0.05)), but did not result in significant reduction of stimulation index, except at (1.0) ng/ml (P<(0.05)); treatment with FTY720 decreased the insulin release at low level (P<(0.05)), but only significantly reduced stimulation index at highest concentration of (1000.0) ng/ml (P<(0.05)). Conclusion Compared to mycophenolic acid, sirolimus and FTY720 demonstrate lower (toxicity) effect on human adult islets in vitro. Choosing low-dose immunosuppressive protocols should be an important rationale for islets transplantation.

关 键 词：FTY720 雷帕霉素 胰岛功能 霉酚酸 成人 胰岛细胞 刺激指数 高糖刺激 免疫抑制方案 释放量 胰岛素 对照组 体外培养 不同浓度 混合培养 药物作用 添加药物 毒性作用 下降 低糖 24h 移植后 低剂量 ml 

分 类 号：R96[医药卫生—药理学]