(523) mg/kg 10

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1 Med J Chin PLA, Vol. 42, No. 1, January 1, [ ] 137 Cs 6.0Gy 8.0Gy 1.01Gy/min C57BL/6 60 (523) mg/kg 10 6d 1 5h 1 1d 1 5h 1 8.0Gy 30d 6.0Gy 30d 8.0Gy 21 30d 50% 20% 30% 6.0Gy 30 (P<0.01) (P<0.05) DNA (P<0.05) (P<0.01) DNA (P<0.01 P<0.05) (P<0.01 P<0.05)30d [ ] [ ] R [ ] A [ ] (2017) [DOI] /j.issn Radioprotective effect of cimitidine on acutely irradiated mice survival and hematopoietic system WANG Qing-rong, ZHANG Jun-ling, HE Ying, SHEN Xian-rong *, JIANG Ding-wen, HOU Deng-yong, LIU Yu-ming, CHEN Wei, LI Ke-xian, LIU Qiong, LUO Qun Department of Protection Medicine, Naval Medical Research Institute, Shanghai , China * Corresponding author, xianrong_sh@163.com This work was supported by the Major Projects of National Science and Technology (2014ZX09J B) [Abstract] Objective To investigate the radioprotective effect of cimetidine on survival rate and hematopoietic system in acutely irradiated mice. Methods The total body irradiation doses were 6.0Gy and 8.0Gy respectively at 1.01Gy/min rate. Sixty healthy male C57BL/6 mice were randomly divided into control group, model group, positive-drug (523) group and cimetidine groups (33.3mg/kg, 100mg/kg and 300mg/kg). Each group had ten mice. The mice were given intragastric administration of cimetidine for 6d before the irradiation in cimetidine groups, and 523 was administered before irradiation once a day for one day in 523 group, and at 5h after irradiation, was given again. The 30d survival rate after 8.0Gy irradiation was recorded. The peripheral blood cells, bone marrow DNA content and frequency of micronucleated polychromatic erythrocytes (fmnpce) were determined 30d after 6.0Gy irradiation. Results After 8.0Gy irradiation, all the mice died on 21th day in model control group. The survival rates in cimetidine groups were 50%, 20% and 30%, respectively. After 6.0Gy irradiation on 30th day, compared with control group, the peripheral white blood cells (WBC) and bone marrow DNA content were decreased significantly (P<0.01, P<0.05) in model group, and fmnpce was increased significantly (P<0.05). Compared with model group, WBC was significantly increased in 300mg/ kg cimetidine group (P<0.01). In cimetidine groups, the bone marrow DNA content was increased significantly after irradiation (P<0.01 or P<0.05), and the fmnpce was decreased significantly (P<0.01 or P<0.05) and tended towards normal. Conclusion Cimetidine could improve 30d survival rate of acutely irradiated mice and has good protective effect on hematopoietic system. [Key words] cimitidine; irradiation injuries, experimental; survival rate; hematopoietic system [ ] (2014ZX09J B) [ ] [ ] ( ) [ ] xianrong_sh@163.com

2 [1] [2] ( ) [3] [4-9] [10-13] [14-16] [15-20] (cimetidine) H 2 [21-23] [24] H Mozdarani [25] 0.25~1.0Gy [26] 2002 Kojma [27] X 137 Cs MEK-5216K Nihon Kohoden BD Biosciences 1.2 C57BL/6 ( 20± 2g 6~8 ) ( ) (CG) (MG) 523 (PG) 33.3mg/kg (CMTDL) 100mg/kg (CMTDM) 300mg/kg (CMTDH) 6d 1 1d 1 2h 137 Cs 6.0Gy 8.0Gy 1.01Gy/min 5h d 8.0Gy 30d Gy 30d = / Gy 30d 20 l (RBC) (PLT) (WBC) 1.6 DNA 6.0Gy 30d 5mmol/L CaCl 2 5ml 4 30min 600 g 10min 0.2mol/L HClO 4 4ml 90 15min 600 g 10min 4 260nm l 1.5ml EP 0.2ml 5ml 5min 300 g 10min 0.06mol/L Sorensen :A :B 4:8:32 (ph 7.2)1ml 30min 1ml 0.2ml 0.06mol/L Sorensen (ph 6.8)0.5ml 300 g 10min 1 PBS 0.5ml 1.8 SPSS 17.0 x±s t P<0.05

3 Med J Chin PLA, Vol. 42, No. 1, January 1, d 8.0Gy d 30d 50% 20% 30%( 1) Survival rate (%) CG PG CMTDM NG CMTDL CMTDH Days after irradiation 1 30d Fig. 1 The 30d survival rate of mice Gy (P<0.05 P<0.01) ( 1) 1 ( x±s n=10) Tab. 1 Effect of cimitidine on the organ index of irradiated mice (x±s, n=10) Group Spleen index Liver index Thymus index CG ± ± ± MG ± ± ± PG ± ± ± CMTDL ± (1) ± ± CMTDM ± (2) ± ± CMTDH ± (1) ± ± (1)P<0.05, (2)P<0.01 compared with model group (MG) Gy 30 WBC PLT (P<0.05 P<0.01) WBC (P<0.01) (P>0.05 2) WBC 2.4 DNA 6.0Gy 30 DNA (P<0.05) 2 (x±s n=10) Tab. 2 Effect of cimitidine on the peripheral blood cell and the frequency of micronucleated polychromatic erythrocytes (fmnpce) of irradiated mice (x±s, n=10) Group WBC( 10 9 /L) RBC( /L) PLT( 10 9 /L) fmnpce CG 2.99± ± ± ± MG 1.83± 0.45 (2) 9.42± ± 64.3 (2) 0.037± (1) PG 1.87± 0.55 (2) 9.54± ± 52.3 (2) 0.034± (2) CMTDL 2.45± ± 0.44 (1) 631.5± 82.1 (2) 0.013± (3) CMTDM 2.12± 0.51 (1) 9.72± ± (1) 0.017± (3) CMTDH 2.87± 0.66 (4) 9.50± 0.30 (1) 662.7± 67.4 (2) 0.016± (3) fmnpce. Frequency of micronucleated polychromatic erythrocytes. (1)P<0.05, (2)P<0.01 compared with control group (CG); (3)P<0.05, (4)P<0.01 compared with model group (MG) DNA (P<0.05 P<0.01 2) DNA 0.70 (2)(4) (3) (1) (4) (3) CG MG PG CMTDL CMTDM CMTDH Group 2 DNA (x±s n=10) Fig. 2 Effect of cimitidine on the content of DNA in bone marrow of irradiated mice (x±s, n=10) OD 260 (1)P<0.05, (2)P<0.01 compared with control group (CG); (3) P<0.05, (4)P<0.01 compared with model group (MG)

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