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西咪替丁对低剂量率60Co γ射线累积照射大鼠损伤的保护作用
作者:张俊玲 何颖 沈先荣 蒋定文 王庆蓉 侯登勇 刘玉明 李珂娴 陈伟 罗群 
单位:200433  上海 海军特色医学中心防护医学研究室(张俊玲、何颖、沈先荣、蒋定文、王庆蓉、侯登勇、刘玉明、李珂娴、陈伟、罗群) 
关键词:西咪替丁 低剂量率照射 辐射防护 
分类号:R631;R641
出版年,卷(期):页码:2019,44(10):823-830
摘要:

 [摘要]  目的  探讨西咪替丁对低剂量率60Co γ射线累积照射大鼠损伤的保护作用。方法  6~8周龄健康雄性SD大鼠60只,随机分为正常对照组、模型组、阳性对照组(89.0 mg/kg香菇多糖),以及低、中、高剂量西咪替丁组(23.370.0210.0 mg/kg西咪替丁),每组10只。除正常对照组外,其余各组大鼠采用60Co γ射线全身照射至累积剂量0.5 Gy,剂量率3.228 mGy/h。末次照射结束后24 h,检测各组外周血细胞计数、骨髓DNA含量、骨髓红细胞微核率(fMNPCE)、骨髓有核细胞数、精子数量、睾丸组织病理学改变、性激素水平,以及血清超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)、过氧化氢酶(CAT)活性和丙二醛(MDA)含量。结果  与正常对照组比较,模型组外周血白细胞、淋巴细胞、粒细胞计数,以及骨髓DNA含量、有核细胞数均减少(P<0.05)fMNPCE明显升高(P<0.01),精子数量、睾酮(T)、促卵泡激素(FSH)和促黄体生成素(LH)水平均明显降低(P<0.05P<0.01),雌二醇(E2)含量明显增加(P<0.05)SODGPxCAT活性均明显降低(P<0.05P<0.01)MDA含量明显增加(P<0.01),显示造模成功。与模型组比较,阳性对照组大鼠骨髓DNA含量和血清T水平明显增加(P<0.05),抗氧化酶SODGPxCAT活性明显升高(P<0.05P<0.01)fMNPCEMDAE2含量明显降低(P<0.05P<0.01);西咪替丁组外周血淋巴细胞计数及骨髓DNA含量明显增加(P<0.01)fMNPCEE2MDA含量均降低(P<0.05)TFSHLH水平均增高(P<0.05),抗氧化酶SODGPxCAT活性均明显升高(P<0.05),睾丸组织结构损伤减轻,精子数量增加,但差异无统计学意义。结论  西咪替丁能减轻低剂量率60Co γ射线累积照射大鼠的机体损伤,可作为潜在的辐射防护药物。

 [Abstract]  Objective  To investigate the protective effects of cimetidine on rats with low dose rate (LDR) 60Co γ-ray cumulative irradiation. Methods  Sixty male SD rats (6-8 weeks old) were randomized into 6 groups (10 each): normal control group, model group, positive control group (89.0 mg/kg lentinan), low-dose cimetidine group (23.3 mg/kg cimetidine), medium-dose cimetidine group (70.0 mg/kg cimetidine), and high-dose cimetidine group (210.0 mg/kg cimetidine). Except for rats in normal control group, the rest rats were irradiated with 60Coγ-ray to a cumulative dose of 0.5 Gy with a dose rate of 3.228 mGy/ h. Twenty-four hours after the last irradiation, peripheral blood cells, bone marrow DNA content, frequencies of micronucleated polychromatic erythrocytes (fMNPCE), bone marrow nucleated cells, sperm count, testis HE, sex hormones, superoxide dismutase (SOD), glutathione (GPx), catalase (CAT) activity, and malondialdehyde (MDA) content were measured. Results  Compared with normal control group, in model group, WBC, lymphocyte and granulocyte content, bone marrow DNA content and the number of nucleated cells significantly decreased (P<0.05), but fMNPCE increased significantly (P<0.01). In addition, sperm count, testosterone (T), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels significantly reduced (P<0.05 or P<0.01), estradiol (E2) levels significantly increased (P<0.05), SOD, GPx and CAT activities significantly decreased (P<0.05 or P<0.01), and MDA levels significantly increased (P<0.01). Rat models were established successfully. Compared with model group, in positive control group, the bone marrow DNA content and T content significantly increased (P<0.05), antioxidant enzyme activity of SOD, GPx and CAT significantly increased (P<0.05 or P<0.01), while the contents of fMNPCE, MDA and E2 significantly reduced (P<0.05 or P<0.01). In the cimetidine-treated groups, the blood lymphocyte number and bone marrow DNA content significantly increased (P<0.01), the activity of antioxidant enzymes SOD, CAT, GPx, T, FSH and LH increased, and the content of fMNPCE, E2 and MDA decreased, the damage of testicular tissue structure decreased (P<0.05), and the number of sperm increased, but there has no statistic significance. Conclusion  Cimetidine, as a potential radiation protection drugs, could effectively improve the rat injury with low-dose-rate 60Coγ-ray cumulative irradiation.

基金项目:
国家科技重大专项课题(2004ZX09J14103-07B)
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