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目的通过研究纳米雄黄的蓄积毒性,为临床用药安全提供依据。方法急性毒性实验:将60只昆明小鼠随机分为6组,每组10只,钠米雄黄5个剂量组按63、126、252、504和1008 mg·kg-1递增剂量灌胃,对照组给予0.5%羧甲基纤维素钠溶液,观察14 d,统计死亡数,计算半数致死量(LD50);蓄积毒性实验:将60只昆明小鼠随机分2组:实验组和对照组,实验组采用递增剂量法给药,每期灌胃剂量依次为31、47、70和105 mg·kg-1,4 d为1期,共5期;对照组用0.5%羧甲基纤维素钠溶液灌胃。观察各组实验中小鼠的临床变化,统计蓄积系数k、体质量变化,对病理组织进行观察,血液生化指标进行检测。结果口服纳米雄黄的LD50为310.25 mg·kg-1,其95%可信区间为231.79~415.24 mg·kg-1;k为3.26,死亡小鼠尸检肉眼观察胸腔、腹腔出现积血,肺脏、肝脏充血,小肠部分坏死;显微镜下发现,纳米雄黄组小鼠心肌出现断裂,肝细胞不典型增生,肺泡结构破坏;血液中尿素、总胆固醇、谷丙转氨酶和对照组比较有极显著升高(P<0.01)。结论纳米雄黄有明显蓄积毒性,临床用药应注意其较高的风险。
Objective To study the accumulation toxicity of nano-realgar to provide the basis for clinical drug safety. Methods Acute toxicity test: Sixty Kunming mice were randomly divided into 6 groups with 10 mice in each group. The 5 doses of Naimixionghuang were given intragastrically at doses of 63, 126, 252, 504 and 1008 mg · kg-1, respectively. Group were given 0.5% sodium carboxymethyl cellulose solution, observed 14 d, the number of statistical death, calculate the median lethal dose (LD50); cumulative toxicity test: 60 Kunming mice were randomly divided into two groups: the experimental group and the control group, the experiment The rats in the control group were treated with 0.5% sodium carboxymethyl cellulose solution Gavage. The clinical changes of mice in each group were observed, the statistical coefficient of accumulation k and body weight were observed, the pathological tissues were observed and the blood biochemical indexes were detected. Results LD50 was 310.25 mg · kg-1. The 95% confidence interval was 231.79-415.24 mg · kg-1. The k was 3.26. The death of mice was observed by naked eyes with pleural and intraperitoneal hematoma, lung and liver Congestion, small intestine necrosis; under the microscope, we found that myocardial rupture, hepatocyte atypical hyperplasia and alveolar structure destruction were found in the nano-realgar group; urea, total cholesterol, alanine aminotransferase in the blood and the control group were significantly increased (P <0.01). Conclusion Nano-realgar has obvious accumulation of toxicity, clinical medication should pay attention to its high risk.