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。
Abstract
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.
关键词
WR2721 /
防护 /
肠型急性放射病 /
机制
Key words
WR2721 /
radioprotection /
intestinal acute radiation sickness /
mechanism
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基金
国家新药创制重大专项(2013ZX09J13102-02C);国家自然科学基金面上项目(81272997)
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