摘要
目的观察Toll样受体5激动剂CBLB502对7.0Gy 60Coγ射线全身照射恒河猴的辐射防护作用。方法 30只健康成年恒河猴分为对症治疗组、WR-2721（辐射防护剂氨磷汀）组和CBLB5022.5、10、40μg/kg组,每组6只。所有动物均用60Coγ射线放射源一次全身双侧照射7.0Gy（剂量率13.00~13.52c Gy/min）。CBLB502给药剂量为2.5、10和40μg/kg,阳性对照药WR-2721剂量为30mg/kg,对症治疗组注射生理盐水0.3ml/kg,均为照射前0.5h一次肌肉注射。所有动物照射后在同一原则下给予对症治疗。观察各组动物一般体征、外周血象、造血祖细胞集落培养情况及组织病理学检查结果。结果照射后40d时CBLB50210、40μg/kg组动物存活率均为100%,而对症治疗组存活率仅为33%（2/6）;WR-2721组各系造血恢复稍快于对症治疗组,但差异无统计学意义;与对症治疗组比较,CBLB50240μg/kg组外周血白细胞和血小板最低值显著增高,血小板低值持续时间缩短,开始恢复时间提前,输血量明显减少（P〈0.05）,骨髓、肠道等组织损伤明显减轻。结论 7.0Gy 60Coγ射线全身照射猴均发生了重度骨髓型急性放射病。照前30min一次性给予40μg/kgCBLB502对7.0Gy 60Coγ射线照射猴有明显的辐射防护作用,其效果优于目前常用的辐射防护剂WR-2721。
Objective A Rhesus monkey model was employed to study the radioprotective effects of a Toll-like receptor 5 agonist, CBLB502, against 7.0Gy whole-body irradiation of 60 Co gamma-rays. Methods Thirty animals were assigned to a placebo treatment group, a WR-2721 positive control group, and three CBLB502 treatment groups（n=6 animals/group）. Each animal was irradiated with 7.0Gy 60 Co γ and given CBLB502 at 2.5, 10 and 40μg/kg, respectively in treatment groups, or WR-2721 at 30mg/kg, or physiological saline 0.3ml/kg for the placebo treatment group. The treatment was given once by intramuscular injection 30 min before irradiation. All irradiated animals received symptomatic treatment based on same guidelines. General observation, peripheral blood tests, hemopoietic progenitor cell colony-counting, and histopathological examination were performed. Results We found that 10 or 40μg/kg CBLB502 treatment resulted in 100% survival, while the survival rate was 33% in placebo treatment group. Hematopoietic recovery in the WR-2721 treatment group was marginally superior to the irradiation control group. Nadirs of peripheral white cell and platelet counts of animals treated with 40μg/kg of CBLB502 were significantly higher than those of the placebo treatment group（P〈0.05）. CBLB502 at 40μg/kg also gave a shortened duration of low platelet count, earlier recovery time, reduced the amount of blood transfusion and damage to the bone marrow and intestine. Conclusion All Rhesus monkeys irradiated with 7.0Gy 60 Co γ-rays would suffer from severe acute radiation sickness of hematopoietic system. CBLB502 at 40μg/kg is radioprotective in thismodel and a single intramuscular injection of CBLB502 in a dose of 40μg/kg 30 min before irradiation gives better radioprotective effects than WR-2721.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2015年第4期285-291,共7页
Medical Journal of Chinese People's Liberation Army
基金
全军医学科技重大专项课题(2008ZXJ09001-004)~~
关键词
辐射损伤
实验性
辐射防护剂
鞭毛蛋白
急性放射病
氨磷汀
radiation injuries, experimental
radiation-protective agents
flagellin
acute radiation sickness
amifostine
