【作者】 沈亚菊；

【导师】 郭定宗；

【作者基本信息】 华中农业大学 ， 临床兽医学， 2006， 硕士

【摘要】 砷是一种剧毒的类金属，能引起机体急性和慢性损伤包括皮肤损害、角化过度、黑脚病、癌症。到目前为止，人类对砷的毒性作用机制还不是很清楚，但存在多种假设：氧化应激，影响细胞增殖，产生基因毒性如影响DNA甲基化、协同致癌、肿瘤促发等。氧化性损伤被认为在砷诱导的毒性损伤和致癌过程中扮演重要角色。近年来，有机砷制剂被广泛应用于畜禽生产，三氧化二砷成功应用于治疗多个早幼粒细胞白血病病例。为了防止砷制剂的滥用和保护人畜健康，更好地评估砷暴露及应用砷制剂治疗疾病的风险，本研究通过体内体外两组试验观察三氧化二砷对小鼠骨髓细胞的抗氧化能力及增殖活性的影响作用。 试验一：50只小鼠随机分成5组，分别以不同浓度的三氧化二砷水溶液（0、5、20、80、320mg／L）灌胃染毒3个月，观察三氧化二砷对小鼠骨髓细胞抗氧化能力、血液学指标及脏器系数的影响。试验二：取正常小鼠的骨髓细胞做体外培养，MTT法检测三氧化二砷对骨髓细胞增殖活性的作用。 试验一的结果如下：（1）20、80和320mg／LAs₂O₃组小鼠骨髓细胞中GSH-Px活性、SOD活性及GSH含量极显著升高（P＜0.01）；5mg／L As₂O₃组GSH-Px活性极显著降低（P＜0.01），SOD活性及GSH含量与对照组差异不显著；各染砷组小鼠骨髓细胞中MDA含量极显著高于对照组（P＜0.01）；5mg／L As₂O₃组小鼠骨髓细胞中ROS活力和抗超氧阴离子自由基活力极显著高于对照组（P＜0.01），20、80和320mg／L As₂O₃组与对照组差异不显著。（2）染砷组小鼠的肝脏系数均极显著高于对照组（P＜0.01）；20、80和320mg／L As₂O₃组小鼠心脏系数显著高于对照组（P＜0.05），肺脏系数极显著高于对照组（P＜0.01）。（3）20和320mg／L As₂O₃组小鼠的红细胞数显著低于对照组（P＜0.05）；20mg／L As₂O₃组小鼠白细胞数显著低于80和320mg／LAs₂O₃组（P＜0.05）；5、20和320mg／L As₂O₃组小鼠的血红蛋白量显著低于对照组（P＜0.05）。试验二的结果如下：随着砷浓度的增加，小鼠骨髓细胞增殖活力先上升后下降。20μmol／L组OD值显著高于对照组（P＜0.05）。 试验一的结果提示：5mg／L三氧化二砷能降低小鼠骨髓细胞抗氧化能力，20mg／L及以上浓度的三氧化二砷能使骨髓细胞抗氧化损伤系统整体激活，细胞中抗氧化酶活性增强，活性氧活力和过氧化脂质被控制在一定水平，骨髓细胞的防御反应增强。试验二的结果表明：在一定浓度范围内三氧化二砷刺激体外培养的小鼠骨髓细胞增殖，超过该范围三氧化二砷对细胞的促增殖作用消失。更多还原

【Abstract】 Arsenic, which is a highly poisonous metalloid, causes acute and chronic adverse health effects, including skin lesions, hyperkeratosis, blackfoot disease and cancer. The exact mechanism of the action of arsenical toxicity is not known clearly, but several hypotheses have been proposed. Oxidative stress, altered cell proliferation, genotoxicity including altered DNA methylation, co-carcinogenesis, and tumor promotion are the potential mechanisms, as described previously. Oxidative damage has been found to play an important role in the arsenic-induced toxicity and carcinogenicity of many organisms. Recently, organic arsenic has been widely used in livestocks production, and arsenic trioxide has been successfully employed in the treatments of the majority of cases of acute promyelocytic leukemia （APL）. A better understanding of the action of arsenic on marrow cells will make a more confident assessment of the risks associated with arsenical therapy and arsenical exposure. With the purpose of preventing drug abuse and protecting human health, we observed the effect of As₂O₃ on antioxidant abilities and proliferative activities of marrow cells in vivo and vitro.In the first experiment, fifty rats were separated randomly into five groups of ten rats each, and were respectively administered via ig the water containing arsenic （0, 5, 20, 80 and 320 mg/L） for three months. Then the antioxidant abilities of marrow cells, hemanalysis parameters of peripheral blood and viscera coefficients of organs were analyzed after rats were killed. In the second experiment, marrow cells were collected from healthy rats to determine the effect of arsenic on proliferative abilities of marrow cells by MTT method.The results of the first experiment were as follows: （1） Compared with the control group, the activities of GSH-Px and SOD as well as the content of GSH in rat marrow cells increased remarkably in 20, 80 and 320 mg/L As₂O₃ groups （P<0.01）; but the activity of GSH-Px decreased significantly in 5 mg/L As₂O₃ group （P<0.01）. The activity of SOD and the content of GSH in 5 mg/L As₂O₃ group did not differ from the control group. The content of MDA in rat marrow cells from arsenic treated group was significantly higher than that of the control group （P<0.01）. The levels of ROS and anti-superoxide anion radical in rat marrow cells from 5 mg/L As₂O₃ group were higher更多还原