氮氧自由基化合物对^60Co γ射线致BALB/c小鼠辐射损伤的防护作用

Radioprotective effects of nitroxide compound NHCOCH3-TEMPO in BALB/c mice

目的 观察氮氧自由基化合物NHCOCH3-TEMPO对雄性BALB/c小鼠电离辐射损伤的防护效果。方法 将120只雄性BALB/c小鼠按随机数字表法分成4和7 Gy照射组,每组60只,每组再按随机数字表法分成6组,每组10只,分别为生理盐水对照组、生理盐水照射组、低剂量TEMPO照射组、中剂量TEMPO照射组、高剂量TEMPO照射组和阳性对照（WR-2721）组。^60Co γ射线照射前0.5 h动物腹腔注射防护药物,剂量分别为：WR-2721组200 mg/kg、低、中、高剂量TEMPO组分别为100、200和400 mg/kg、生理盐水对照组和生理盐水照射组给予等量生理盐水。4 Gy全身照射组用于观察小鼠照后8和15 d骨髓有核细胞数、骨髓DNA含量和外周血象的变化;7 Gy全身照射用于观察小鼠照后30 d生存率。结果 4 Gy照射后,TEMPO预处理组小鼠骨髓有核细胞计数、骨髓DNA含量较生理盐水照射组均明显增加（t=2.53-6.13,P〈0.05）;中剂量TEMPO预处理组小鼠外周血白细胞数较生理盐水照射组明显增加（t=4.34,P〈0.05）,但外周血红细胞数与生理盐水照射组相比,差异无统计学意义。7 Gy照射后,低剂量TEMPO预处理组小鼠30 d存活率较生理盐水照射组明显增加（χ^2=5.934,P〈0.05）。结论 氮氧自由基化合物NHCOCH3-TEMPO对雄性BALB/c小鼠γ射线辐射损伤有一定的防护作用。

Objective To investigate the protective effects of nitroxide compound NHCOCH3-TEMPO against γ-ray irradiation-induced injury in male BALB/c mice. Methods 120 BALB/c male mice were randomly divided into two super group, each super group then were randomly divided into 6 groups：control group, normal saline（NS）＋γ group, low-dose TEMPO＋γ group, middle-dose TEMPO＋γ group, high-dose TEMPO＋γ group and the positive control （WR-2721）＋γ group. BALB/c mice were intraperitoneally injected with nitroxide compound at 0.5 h before whole body ^60Co γ-ray irradiation. The drug dosages were as follows：WR-2721 group 200 mg/kg, low-dose TEMPO group 100 mg/kg, middle-dose TEMPO group 200 mg/kg, high-dose TEMPO group 400 mg/kg. The first super group of the mice was given 7 Gy γ-ray whole-body irradiation, and then 30 d survival rate was observed. The second super group of the mice was given 4 Gy γ-ray whole-body irradiation. The number of nucleated cells and the content of DNA in bone marrow, as well as the blood routine were detected. Results At 8th and 15th day after 4 Gy γ-ray irradiation, the number of bone marrow nucleated cells, the content of DNA significantly increased in TEMPO＋γ-ray groups compared with NS＋γ-ray group（t=2.53-6.13,P〈0.05）. The number of white blood cells significantly increased in middle dose TEMPO＋γ-ray groups compared with NS＋γ-ray group（t=4.34,P〈0.05）, while there was no significant difference in the number of red blood cells between the TEMPO＋γ-ray group and the NS＋γ-ray group. After 7 Gy γ-ray irradiation, the survival rate of mice on the 30th day significantly increased in low-dose TEMPO＋γ-ray group compared with NS＋γ-ray group（χ^2=5.934,P〈0.05）. Conclusions The nitroxide compound NHCOCH3-TEMPO could provide radio protective effects in BALB/c mice.