尼尔雌醇照前多次给药对骨髓型急性放射病小鼠的防护作用及其机制研究

Radiation protection effect and its mechanism of multiple nilestriol administrations on the mice with bone marrow type of acute radiation syndrome

目的 了解抗放药尼尔雌醇照前不同给药方案对60Co γ射线照射所致小鼠骨髓型急性放射病的防护效应的影响,并揭示其促造血恢复机制。方法 采用外周血象分析和存活率实验确定尼尔雌醇较优给药方案,再以骨髓造血干/祖细胞表面标志分析、多系骨髓细胞集落及骨髓HE病理切片等方法,分析尼尔雌醇照前2次间隔给药促进照后骨髓造血恢复的作用机制。结果 尼尔雌醇照前3次间隔给药与2次间隔给药均能提高9.0 Gy照射小鼠存活率至100%,明显优于1次给药（20%, χ^2=21.66、21.66,P〈0.05）。尼尔雌醇照前3次连续给药与2次间隔给药均能改善6.5 Gy照射小鼠外周血白细胞、中性粒细胞、血小板和红细胞的恢复（F=21.33、100.9、49.34、19.19, P〈0.05）,且比1次给药效果好（F=17.11、63.38、21.89、14.37, P〈0.05）。尼尔雌醇2次间隔给药显著提高6.5 Gy照射后小鼠10 d骨髓造血干、祖细胞数（t=8.58、2.80, P〈0.05）;显著增强小鼠骨髓造血细胞集落形成能力,与1次给药相比,差异有统计学意义（t=4.29、6.34, P〈0.05）。同时,2次间隔给药明显改善照射小鼠骨髓象的重建。结论 与传统的照前单次给药相比,尼尔雌醇照前多次给药可显著提升其对小鼠骨髓型急性放射病的辐射防护效果。考虑到核医学应急救援的实际情况,建议尼尔雌醇照前采用间隔1 d的给药方式,在减少尼尔雌醇给药次数情况下,以获得最佳的抗放效果。

Objective To understand the radiation protection effect of pre-irradiation administrations of nilestriol on the mice with bone marrow type of acute radiation syndrome after irradiation with 60Co γ-rays, along with its mechanisms for improvement of hematopoiesis. Methods The nilestriol administration protocols were prepared by analysis of peripheral blood cell counts and survival rate experiment on mice. The mechanisms by which the pre-irradiation twice administrations improved the post-irradiation recovery of bone marrow hematopoiesis were studied by the analysis of the surface marker of bone marrow hematopoietic stem/progenitor cells of mice and by the inspection of hematopoietic progenitor cell colony and by using histopathological assessment of bone marrow. Results Pre-irradiation administration of nilestriol at two-or three-day intervals had been shown to increase survival rates up to 100% in mice exposed to 9.0 Gy γ-rays, which was superior to a single administration （20%, χ^2=21.66, 21.66, P〈0.05）. The pre-irradiation administration both at one-day or two-day intervals were capable of improving the recovery of peripheral blood counts, including white blood cell （WBC）, red blood cell （RBC）, and platelet in mice exposed to 6.5 Gy （F=21.33, 100.9, 49.34, 19.19, P〈0.05）, showing the better effects than a single administration （F=17.11, 63.38, 21.89, 14.37, P〈0.05）. The two-day-interval administration of nilestriol could significantly increase the numbers of bone marrow hematopoietic stem/progenitor cell counts （t=8.58, 2.80, P〈0.05） in mice on day 10 after 6.5 Gy irradiation. This also could be capable to significantly improve colony formation, with there being statistical difference compared with single administration（t=4.29, 6.34, P〈0.05）. Also the administration at two-day-interval were also usefull in reconstruction of hematopoietic cell hyperplasia of bone marrow of irradiated mice. Conclusions As compared with conventional single admination, the pre-irradiation multiple administrations of nilestriol showed significantly improved radiation protection effects. Considering a nuclear medical emergency rescue, it is recommended to follow the pre-irradiation administration of nilestriol at two-day interval, which could obtain the best protection effects at minimum administration frequency.