克方的急性毒性和长期毒性实验研究
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篇名: 克方的急性毒性和长期毒性实验研究
TITLE:
摘要: 目的:考察克方的急性毒性和长期毒性,为其临床试验与合理用药提供参考。方法:将20只ICR小鼠随机分为克方组(350 g/kg)和正常对照组(饮用水),每组10只,每天ig给药2次(间隔8 h),连续14 d,进行急性毒性实验。将120只SD大鼠随机分为正常对照组(饮用水)和克方高、中、低剂量组[5、2.5、1.25 g(生药)/ml],每组30只(♀♂各半),每天ig给药2次(间隔8 h),连续12周,进行长期毒性实验。结果:克方最大耐受量为350 g/kg,相当于临床人用量的140倍。与正常对照组比较,克方高剂量组大鼠体质量增长缓慢、摄食量减少(P<0.05或P<0.01);雄性大鼠血中红细胞分布宽度、血红蛋白含量分布宽度、平均血红蛋白浓度降低,血小板平均体积、网织红细胞升高(P<0.05或P<0.01),但均在本实验室正常生理值范围内;克方高剂量组大鼠血中尿素氮、总胆红素、天冬氨酸转氨酶、丙氨酸转氨酶活性升高(P<0.05或P<0.01),恢复期大鼠未见异常;给药12周后,克方中、低剂量组大鼠凝血酶原时间缩短(P<0.05或P<0.01);克方高剂量组发现8只大鼠膀胱黏膜上皮细胞轻、中度变性和坏死、脱落,恢复期无异常。结论:克方在临床140倍用量下对小鼠未见明显毒性作用。克方连续重复给药12周后,对大鼠肝脏、肾脏代谢有影响;具有一定的可逆性膀胱毒性;恢复期大鼠各项检查未见病变加深或迟发性病变。
ABSTRACT: OBJECTIVE: To investigate acute toxicity and long-term toxicity of Kefang (KF), and to provide reference for clinical trial and rational drug use. METHODS: 20 ICR mice were randomly divided into KF group (350 g/kg) and normal control group (drinking water), with 10 mice in each group; they were given relevant medicine intragastrically, twice a day (every 8 h), for consecutive 14 d; acute toxicity test was conducted. 120 SD rats were randomly divided into normal control group (drinking water), KF high-dose, medium-dose and low-dose groups [5, 2.5, 1.25 g (crude drug)/ml], with 30 rats in each group (half male and half female); treatment groups were given relevant medicine intragastrically twice a day (every 8 h), for consecutive 12 weeks; long- term toxicity was conducted. RESULTS: The maximum tolerated dose of KF was 350 g/kg, which was equal to 140 times as clinical human dosage. Compared to normal control group, body weight of rats in KF high-dose group increased slowly and food intake decreased (P<0.05 or P<0.01); red blood cell distribution width(RDW), hemoglobin distribution width (HDW), mean hemoglobin concentration(MCHC)of male rats were all decreased, while mean platelet volume (MPV) and reticulocyte (RET) were increased (P<0.05 or P<0.01); these indicators were all in normal physiological range of our laboratory. BUN, TBIL, AST and ALT acitivies of KF high-dose groups increased (P<0.05 or P<0.01), and no abnormal change was found during recovery period; 12 weeks after medication, prothrombin time of KF medium-dose and low-dose groups shortened (P<0.05 or P<0.01); mild and middle degeneration and necrosis, denudation of bladder epithelial cells were found in 8 rats of KF high-dose group, no abnormality was found during recovery period. CONCLUSIONS: There was no obvious toxic effect on the mice in the dose of 140 times of the clinical dose. Continuous 12-week administration of KF will influence liver and renal metabolism of rats; KF shows reversibility toxicity to bladder. No deeper lesions or delayed lesions is found in rats during recovery period.
期刊: 2016年第27卷第34期
作者: 张光际,杨凡,时乐,尹莲,徐立
AUTHORS: ZHANG Guangji,YANG Fan,SHI Le,YIN Lian,XU Li
关键字: 克方;急性毒性;长期毒性;大鼠;小鼠
KEYWORDS: Kefang; Acute toxicity; Long-term toxicity; Rat; Mice
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