实用器官移植电子杂志 ›› 2018, Vol. 6 ›› Issue (2): 103-107.

• 论著 • 上一篇    下一篇

雷帕霉素衍生物对胰岛的毒性研究

张娟1,2,3,付嘉钊1,2,4,王路敏1,2,李艳萍1,2,江红5,夏俊杰1,2,齐忠权1,2,6   

  • 出版日期:2018-03-20 发布日期:2021-06-24

The toxicity of rapamycin derivatives on islet

  • Online:2018-03-20 Published:2021-06-24

摘要:

目的 探讨雷帕霉素及其衍生物依维莫司、地磷莫司、佐他莫司对胰岛的毒性作用。 方法 采用小鼠胰岛素瘤细胞(MIN6)作为体外研究胰岛细胞的对象,分别在含有依维莫司、地磷莫司、 佐他莫司的培养基中孵育 MIN6 细胞 48 小时,通过 Brdu 检测细胞增殖、CCK8 检测细胞活力、PI 检测细胞 周期、流式细胞术检测细胞凋亡以及 ELISA 检测细胞分泌胰岛素功能,观察 3 种雷帕霉素衍生物对 MIN6 细胞的影响。结果 我们发现 3 种雷帕霉素衍生物均会对 MIN6 细胞的增殖和活力产生抑制作用。在细胞 周期和凋亡实验中,与阴性对照组比较,3 种衍生物对 MIN6 细胞的影响呈现抑制 G1 期向 S 期转变的趋势 和促进细胞凋亡的趋势,但差异没有统计学意义。另外,3 种衍生物与雷帕霉素一样,均可减少 MIN6 细胞 分泌胰岛素,差异具有统计学意义。结论 雷帕霉素及其衍生物依维莫司、地磷莫司、佐他莫司均对胰岛 产生一定毒性。

Abstract:

Objective To investigate the toxic effects of rapamycin and its derivatives, everolimus, cefotiam, zotarolimus on islets. Methods Experiments were performed on mouse insulinoma cells(MIN6)cells. MIN6 cells were cultured in a medium containing everolimus, diphospholimus, and zotarolimus for 48 hours, and cell proliferation was detected by Brdu. Cell viability was detected by CCK8, cell cycle was detected by PI, cell apoptosis was detected by flow cytometry, and insulin secretion by cells was detected by ELISA. The effects of three rapamycin derivatives on MIN6 cells were observed. Results We found that rapamycin derivatives impaired cell proliferation and viability. In the cell cycle and apoptosis experiments, the effect of three derivatives on MIN6 cells compared with the negative control, showed the trend of inhibited G1 phase to S phase transition and promoted apoptosis,but the difference had not statistically significant. So did Apotosis experiment. Morever,rapamycin derivatives treatment of MIN6 cells resulted in a loss of cell insulin secretion,the difference had statistically significant. Conclusion This report provides evidence that rapamycin derivatives ,as the same as the rapamycin ,had toxicity to islets.