免疫抑制剂对人胰岛细胞的毒性作用

Studies on the toxicity of immunosuppressive agent to human islet cells in vitro

目的探讨临床常用免疫抑制剂对人胰岛细胞的直接毒性作用。方法应用体外分离纯化后培养的人胰岛细胞,以刺激系数和丫啶橙/碘丙啶染色为效应指标,检验低、中、高不同浓度免疫抑制剂对人胰岛细胞的直接毒性作用。结果体外培养3天后,低浓度免疫抑制剂未表现出胰岛毒性作用;中浓度免疫抑制剂对胰岛的毒性不同,以他克莫司为重;高浓度免疫抑制剂有较强的胰岛毒性。结论免疫抑制剂对人胰岛细胞直接毒性作用与浓度相关,选择低胰岛毒性免疫抑制方案有助于提高胰岛移植成功率。

Objective To evaluate the direct deleterious effect of irnmunosuppressive agent to human islets, and to explore the suitable immunosuppressive protocol for human islet transplantation. Methods Human islet cells cultured in vitro were exposed to various therapeutic concentrations of four immunosuppressive agents for 72h respectively. Glucose-stimulating insulin secretion during incubation was measured using the ultrasensitive human insulin ELISA kit. The assessment of islet cell viability was studied with acridine orange （AO）-propidium iodide （PD. Results In vitro, low therapeutic concentrations had no deleterious effect on insulin secretion or viability of islet, but high concentration of the drugs was deleterious to β-cell survival as well as insulin secretion. The effect of medium concentration varied significantly, and sirolimus tacrolimus demonstrated stronger deleterious effect on human islets than mycophenolic acid. Conclusion The direct deleterious effect of immunosuppressive agents to islet cells is dose-dependent, therefore immunosuppressive agent must be opti- mized after islet transplantation.