氨磷汀对小鼠肠型急性放射病的防护作用及其机制

 目的 研究氨磷汀(amifostine, WR2721)对小鼠肠型急性放射病的防护作用及其机制。方法 建立小鼠肠型急性放射病模型。C57BL/6J小鼠随机分为对照组和WR2721给药组,接受15 Gy ⁶⁰Co-γ全身照射,照后移植健康小鼠骨髓细胞,观察小鼠受照后30 d的存活率和平均生存时间,以及用隐窝细胞微克隆实验,研究照后3.5 d隐窝细胞数量及小肠黏膜情况。结果 对照组小鼠均在10 d内死亡,WR2721给药组存活率提高到80%;对照组和WR2721给药组平均隐窝数分别为(6.1±0.7)个、(28.0±1.1)个,差异有统计学意义(P<0.0001);对照组和WR2721给药组绒毛高度分别为(51.48±2.04)μm、(73.29±3.24)μm,差异有统计学意义(P<0.0001)。结论 WR2721对肠型急性放射病小鼠有保护作用,通过提高隐窝干细胞增殖活性,促进黏膜的恢复,提高小鼠的存活率。

Protective effect and mechanism of amifostine on intestinal acute radiation sickness

Objective To study the radioprotection effect and mechanism of amifostine (WR2721) on intestinal acute radiation sickness. Methods Based on the intestinal acute radiation sickness model, C57BL/6J mice were randomly divided into control group and group WR2721. Bone marrow cells from healthy mice were transplanted after 15 Gy ⁶⁰Co-γ shielded body irradiation. Then the survival rate in 30 d after irradiation, and the number of proliferative crypt cells and the small intestine mucosa situation with micro-cloning survival assay of mouse crypt cells at 3.5d post-irradiation were observed . Results The mice in control group died within 10 days, survival rate in WR2721 administrered group increased to 80%; in the control group and WR2721 drug group, the average number of crypts were 6.1±0.7, 28±1.1, the difference was statistically significant (P<0.0001); in control group and WR2721 administered group, villus heights were(51.48±2.04)μm, (73.29±3.24)μm, the difference was statistically significant (P<0.0001). Conclusions WR2721 has significantly radioprotective effect on intestinal acute radiation sickness by improving the survival rate of mice, promoting crypt cells regeneration and protecting the intestinal mucosa.