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作 者:范潇婷 于睿鹏[1] 董瑞娟[1] 罗广彬[1] 马志涛[1] FAN Xiao-ting YU Rui-peng DONG Rui-juan LUO Guang-bin MA Zhi-tao(School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China)
出 处:《中国实验方剂学杂志》2017年第15期118-123,共6页Chinese Journal of Experimental Traditional Medical Formulae
基 金:北京中医药大学自主选题项目--特聘教授启动基金项目(1040053310002/002)
摘 要:目的:比较斑蝥素及去甲斑蝥素对小鼠的毒性作用及两者靶器官损伤程度的差异。方法:取Balb/c小鼠,采用概率单位法计算获得斑蝥素与去甲斑蝥素的半数致死量(median lethal dose,LD_(50))。以1/2 LD_(50)作为毒性研究给药剂量,连续灌胃给药2周。2周后取血检测血清丙氨酸氨基转移酶(ALT),天冬氨酸氨基转移酶(AST),尿素氮(BUN)水平,取肝、肾、小肠和膀胱进行病理组织学观察比较。结果:斑蝥素和去甲斑蝥素LD_(50)分别为2.045,20.966 mg·kg^(-1)。分别以1/2 LD_(50)给药剂量给小鼠灌胃2周后,血清学检测结果表明,与正常组比较,斑蝥素组无显著差异;去甲斑蝥素可导致ALT,BUN水平显著性升高。肝、肾病理结果表明,与正常组比较,斑蝥素组肝肾轻微病变,去甲斑蝥素组可见肝脏炎性细胞浸润,肝细胞空泡变样,肾小球和小管弥漫性损伤。小肠病理结果表明,斑蝥素组导致肠道淋巴结肿大并分叶,去甲斑蝥素组症状较轻。膀胱病理表明,斑蝥素组发现血管炎症、膀胱移行上皮或黏膜层炎症反应,去甲斑蝥素组轻微移行上皮炎症反应。结论:临床前动物模型结果表明,去甲斑蝥素的毒性主要表现在肝脏和肾脏,斑蝥素的毒性作用主要表现为小肠和膀胱。Objective:To compare the toxicities and organ injuries of cantharidin and norcantharidin in mice.Method:Balb/c mice were treated with cantharidin or norcantharidin at different doses for two weeks to determine their median lethal dose(LD50) by the probability unit regression analysis method.Other mice were treated with 1/2 LD50 of the respective drugs for 2 weeks.At the end of the treatment,tissue samples from livers,intestines,kidneys and bladders were collected for pathological analyses.Result:LD50 of cantharidin and norcanditharidin were 2.045 and 20.966 mg·kg-1.Norcantharidin caused significant increases in alanine aminotransferase(ALT) and rea nitrogen(BUN).Norcantharidin caused inflammatory cell infiltration and spongelike change in liver,and injuries in glomeruli and renal tubules.Cantharidin led to increases in intestinal lymph nodes and lobulation in the intestine,vascular,bladder and mucosa inflammations.Conclusion:Treatments with1/2 LD50 dose of norcantharidin and cantharidin led to distinct organ/tissue-specific injuries in mice.Norcantharidin caused severe injuries in liver and kidney,while cantharidin led to severer injuries in intestinal and bladder than norcantharidin.
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