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目的研究1,1-二氨基-2,2-二硝基乙烯(FOX-7)对大鼠的亚慢性经口毒性效应。方法无特定病原体级健康成年SD大鼠随机分为对照组和低、中、高剂量组,每组24只,雌雄各半。3个剂量组分别以10、30和90 mg/(kg·d)体质量FOX-7-水淀粉(水淀粉质量分数为4.0%)混悬液灌胃染毒,1次/d,每周6 d,连续90 d;对照组给予等体积水淀粉溶液灌胃。观察大鼠的中毒表现、体质量、食物利用率、血常规、血液生化指标、脏器系数变化及组织器官的组织病理学改变。结果 1雌性、雄性高剂量组大鼠在染毒第28天后体质量均低于同时间点同性别对照组(P<0.05),在染毒第77和90天食物利用率分别低于同时间点同性别对照组(P<0.05)。2与雌性对照组比较,雌性低、中和高剂量组大鼠红细胞计数、血红蛋白、红细胞压积均下降(P<0.05),雌性高剂量组大鼠血小板计数下降(P<0.05)。与雄性对照组比较,雄性高剂量组大鼠红细胞计数、血红蛋白、红细胞压积和平均红细胞血红蛋白浓度均下降(P<0.05),雄性中和高剂量组大鼠血小板计数均下降(P<0.05)。3与雌性对照组比较,雌性中和高剂量组大鼠血清总胆固醇水平均升高(P<0.05),雌性高剂量组大鼠尿素氮水平升高(P<0.05)。与对照组比较,高剂量组大鼠总蛋白和尿酸水平均升高,而乳酸脱氢酶活力下降(P<0.05)。4雌性高剂量组大鼠脾脏脏器系数高于雌性对照组(P<0.05),雄性中和高剂量组大鼠脾脏脏器系数均高于雄性对照组(P<0.05);高剂量组大鼠肝脏和肾脏的脏器系数均高于对照组(P<0.05);雄性高剂量组大鼠睾丸、附睾的脏器系数均低于雄性对照组(P<0.05),且均出现不同程度的睾丸曲细精管萎缩,精细胞减少。5未观察到有害作用水平在雌性大鼠为小于10.00 mg/(kg·d),雄性大鼠为10.00 mg/(kg·d)。结论在本实验条件下,FOX-7可抑制大鼠的生长发育,引起血液系统及雄鼠的生殖系统损害。
Objective To investigate the subchronic oral toxicity of 1,1-diamino-2,2-dinitroethylene (FOX-7) in rats. Methods Healthy adult SD rats without specific pathogen were randomly divided into control group and low, medium and high dose groups, 24 in each group, male and female. The three dose groups were orally administered with a suspension of 10, 30 and 90 mg / (kg · d) of body weight FOX-7-starch (water-starch mass fraction 4.0%) once a day, 6 d, continuous 90 d; control group was given equal volume of water, starch solution gavage. Observe poisoning performance, body weight, food utilization, blood, blood biochemical indicators, organ coefficient changes and histopathological changes of tissues and organs. Results The body weight of the female and male high-dose groups was lower than that of the same-sex point group on the 28th day (P <0.05), and the food utilization rates on the 77th and 90th day were lower than those of the same time Point same sex control group (P <0.05). Compared with the female control group, the erythrocyte count, hemoglobin and hematocrit of the female low, middle and high dose groups decreased (P <0.05), and the platelet counts of the female high dose group decreased (P <0.05). Compared with the male control group, the red blood cell count, hemoglobin, hematocrit and mean erythrocyte hemoglobin in the male high-dose group were decreased (P <0.05), and the platelet counts in the male middle and high dose group were decreased (P <0.05) . Compared with the female control group, the levels of serum total cholesterol in the female middle-high dose group were significantly increased (P <0.05), while those in the high-dose female group were higher (P <0.05). Compared with the control group, the total protein and uric acid levels of rats in high dose group increased, while the activity of lactate dehydrogenase decreased (P <0.05). The spleen organ coefficient of high dose group was higher than that of female control group (P <0.05), and the coefficient of spleen organ of middle and high dose group was higher than that of male control group (P <0.05) The organ coefficients of liver and kidney in rats were significantly higher than those in control group (P <0.05). The indexes of testis and epididymis in male high-dose group were lower than those in male control group (P <0.05) Testicular seminiferous tubules atrophy, sperm cells decreased. No adverse effects were observed in female rats of less than 10.00 mg / (kg · d) and in male rats of 10.00 mg / (kg · d). Conclusion Under the experimental conditions, FOX-7 can inhibit the growth and development of rats and cause the reproductive system damage of blood system and males.