免疫抑制剂依维莫司对大鼠胰岛细胞的毒性作用

Toxic Effect of Immunosuppression Agent Everolimus on Insuloma Cells and Pancreatic Islets of SD Rat

目的观察依维莫司等免疫抑制剂对大鼠胰岛瘤细胞(INS-1)和SD大鼠正常胰岛细胞代谢活性和功能的影响,旨在探讨依维莫司在胰岛移植免疫抑制治疗中的安全性和可行性。方法不同浓度梯度免疫抑制剂依维莫司、西罗莫司、环胞霉素A和霉酚酸酯处理INS-1和正常胰岛细胞,用MTT法检测细胞的代谢活性;用葡萄糖刺激胰岛素分泌实验检测胰岛细胞的胰岛素分泌功能。结果临床血药浓度以上的依维莫司和西罗莫司高浓度组胰岛细胞增殖抑制率低于环胞霉素A和霉酚酸酯(P<0.05);依维莫司在临床血药浓度范围和其它免疫抑制剂一样可以抑制胰岛细胞的胰岛素分泌功能,各组间的刺激指数差异无统计学意义。结论依维莫司和西罗莫司对INS-1细胞及SD大鼠胰岛的毒性作用较小,环胞霉素A和霉酚酸酯对INS-1和SD大鼠胰岛具有较为明显的毒性作用,依维莫司有望作为新型免疫抑制剂应用于临床胰岛移植。

Objective To investigate the effect of immunosuppression agent Everolimus on the viability and function of insuloma cells （INS-l） and pancreatic islet cells cultured in vitro. Methods INS-1 cells and islets were treated with a series of concentrations of immunosuppression agents （Everolimus, Cyclosporin A, Sirolimus and Mycophenolate Mofetil）. The viability of INS-1 ceils and rat pancreatic islets were determined with MTT and the function of INS-1 cells and rat pancreatic islets was evaluated with Glucose-stimulated insulin secretion assay. Results Above the clinical blood concentration, the inhibition rate of islet cell proliferation in the high concentration group of Everolimus and Sirolimus was significantly lower than that of Cyclosporin A and Mycophenolate Mofetil group （P〈 0. 05）t Everolimus in the blood drug level, like other immunosuppressive agents, can inhibit the function of insulin secretion, and the stimulation index of each group was no significant difference. Conclusion Compared to Mycophenolate Mofetil and Cyclosporin A, Everilimus and Sirolimus demonstrate lower toxicity effect on INS-1 cells and rat pancreatic islets in vitro and Everolimus is expected as a new type of immunosuppressive agent used in clinical islet transplantation.