西咪替丁对低剂量辐射比格犬的保护作用

Radioprotective Effect of Cimetidine on Low-dose Irradiated Beagle Dogs

目的观察西咪替丁对低剂量电离辐射比格犬的保护作用。方法雄性比格犬24只,共6组,每组4只,分别为正常对照组,模型对照组,阳性药对照组,西咪替丁低、中、高剂量组(5.33、10.67、21.33mg·kg^(-1)),采用60 Coγ射线连续全身照射23d,剂量率为0.0408mGy·min^(-1)。西咪替丁于照射期间连续灌胃给药,每天1次。分别于累积照射剂量为0.2、0.4、0.6、0.8和1.0Gy时,检测外周血象,并在累积照射剂量为1.0Gy时检测CD34^+细胞、血清中抗氧化酶和丙二醛。结果累积照射期间,各组比格犬的血象检测值均在正常值范围内波动。与正常对照组比较,累积照射1.0Gy后24h,比格犬骨髓造血干细胞数量显著降低(P<0.01),血清中的SOD、CAT、GPx及GST活力显著降低(P<0.01,P<0.05),MDA含量显著升高(P<0.01)。与辐照模型组比较,西咪替丁中剂量组造血干细胞明显升高(P<0.05),各给药组的SOD和CAT活力均显著升高(P<0.01),西咪替丁高剂量组的GPx和GST活力显著升高(P<0.01,P<0.05),西咪替丁中、高剂量组的血清MDA含量显著减少(P<0.01)。结论西咪替丁可有效改善1.0Gyγ射线累积照射比格犬所致的造血干细胞数量减少和抗氧化系统损伤,具有较好的辐射保护作用。

Objective To investigate the radioprotective effect of cimetidine on Low-dose irradiated Beagle dogs.Methods Twenty-four male Beagle dogs were divided into six groups：normal control group,model group,positive control group and cimetidine groups at the dose of 5.33,10.67,21.33 mg·kg^-1 respectively.The dogs were irradiated with 60 Coγ-ray at 0.0408 mGy·min^-1 rate for 23 days.Cimetidine was administered intragastrically during irradiation,once a day.Blood samples were collected and the number of peripheral blood cells was counted at 0.2,0.4,0.6,0.8,1.0 Gy.At 1.0 Gy,the percentages of CD34^＋ cells in bone marrow,antioxidant enzyme and MDA in serum were detected.Results During cumulative exposure,peripheral blood cells in all the irradiated dogs fluctuated in the normal range.Compared with normal control group,serum MDA in irradiated dogs increased significantly（P〈0.01）,while SOD,CAT,Gpx and GST activity,the percentage of CD34^＋ cells in irradiated dogs decreased significantly at 24 hafter1.0 Gy cumulative irradiation（P〈0.01,P〈0.05）.Cimetidine increased the percentage of CD-34＋ cells（P〈0.05）and antioxidant enzyme activity,but decreased the serum MDA content（P〈0.01,P〈0.05）.Conclusion Cimetidine can reverse antioxidant system injury induced by 1.0 Gyγ-ray cumulative exposure,and alleviate the decrease of hematopoietic stem cells in bone marrow.The results have demonstrated that cimetidine has a good protective effect on low-dose irradiated beagle dogs.