摘要
目的:通过对小鼠和大鼠进行急性和长期毒性研究,观察安特逍胶囊对啮齿动物的毒性反应,为其临床安全用药提供依据。方法:采用单次灌胃给药法,其中小鼠采用最大给药剂量法(10. 0 g·kg^(-1)),大鼠设置安特逍胶囊低(1. 0 g·kg^(-1))、中(4. 0 g·kg^(-1))、高(16. 0 g·kg^(-1))剂量组,观察给药后动物出现的急性毒性反应。采用连续灌胃给药法,大鼠设置安特逍胶囊低(0. 25 g·kg^(-1))、中(0. 8 g·kg^(-1))、高(2. 0 g·kg^(-1))剂量组,灌胃给药26周,停药恢复4周,观察大鼠一般状况、体质量、摄食量、体温、眼科、心电图、血液学及血清生化学指标,大体解剖及组织病理学变化。结果:急性毒性研究中,小鼠灌胃安特逍胶囊最大耐受量为10. 0 g·kg^(-1),SD大鼠最大耐受量为4. 0,16. 0 g·kg^(-1)灌胃可导致大鼠体质量及摄食量降低。长期毒性研究中,安特逍胶囊高剂量组共2只大鼠因胃功能受损死亡,各剂量组雄鼠体质量出现降低,停药后可渐恢复。给药组个别动物的血液学、血凝和血清生化指标出现变化,但无剂量相关性,应属正常波动。脏器系数及脏脑系数无明显异常。组织病理学检查发现给药14周及26周,安特逍胶囊中、高剂量组大鼠的胃出现不同程度皮胃和腺胃交界处黏膜下层和(或)腺胃黏膜下层内单核细胞浸润的病变。结论:安特逍胶囊对小鼠无毒副作用,但高剂量用药时能够导致SD大鼠胃功能受损,提示临床需特别关注安特逍胶囊可能导致的胃毒性。
Objective: To observe the toxic reaction of Antexiao capsules in rodents by acute and long-term toxicity studies in mice and rats to provide basis for clinical safe medication. Methods: ICR mice were administered the drug with a maximum acceptable oral dose,and rats were orally treated with the drug at the dose levels of 1. 0,4. 0 g·kg-1 and 16. 0 g·kg-1 to observe the acute toxic reaction of Antexiao capsules in animals. In the chronic toxicity study,rats were orally treated with Antexiao capsules at the doses of 0. 25,0. 8 and 2. 0 g·kg-1 for 26 weeks and observed for four weeks after administration. Clinical observations,body weights,body temperature,food consumption,electrocardiogram,ophthalmoscopy,hematology,blood biochemistry and histopathological findings were examined. Results: In the acute toxicity test,the maximum tolerance dose in mice was 10. 0 g·kg-1 and that in rats was 4. 0 g·kg-1,while body weight and food intakes of rats in the high dose group were reduced. In the chronic toxicity study,2 rats treated with high dose were died of impaired gastric function. The body weight of male rats in each group decreased significantly (P < 0. 05),no significant changes in ophthalmologic examination,clinical pathology and organ coefficients. The hematological,hemagglutination and serum biochemical of individual animals in the administration group changed,but there was no dose correlation and it should be normal fluctuation. There were no significant abnormalities in organ coefficient and viscera-brain coefficient. Histopathological examination showed varying degrees of mononuclear cells infiltration in either the submucosa of stomach and gland stomach junction or the submucosal layer of glandular stomach in middle dose and high dose groups after 14-and 26-week drug treatment. The changes returned to normal after the recovery period,except for the stomach’s histopathological pathological changes in high dose rats. Conclusion: Antexiao capsules show no toxicity in mice,while it can cause gastrointestinal damage in SD rats at high dose,suggesting attention should be paid to the gastrointestinal toxicity caused by Antexiao capsules.
作者
杜肖
王建农
韩林
孙彩霞
曹晓强
孙建
Du Xiao;Wang Jiannong;Han Lin;Sun Caixia;Cao Xiaoqiang;Sun Jian(Beijing Key Laboratory of Chinese Medicine Pharmacology,Institute of Basic Medical Sciences of Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Guang’anmen Hospital,China Academy of Chinese Medical Sciences)
出处
《中国药师》
CAS
2019年第2期327-332,共6页
China Pharmacist
关键词
安特逍胶囊
白英
白英总甾体生物碱
急性毒性反应
长期毒性反应
Antexiao capsules
Solanum lyratum
Total steroidal alkaloids from Solanum lyratum
Acute toxicity
Chronic toxicity