摘要
目的观察紫蓝素对大鼠的长期毒性反应,为其临床应用提供参考。方法大鼠160只,随机分为对照组和紫蓝素大、中、小剂量组,每组40只。采用大剂量(2000mg·kg^-1·d^-1)、中剂量(200mg·kg^-1·d^-1)、小剂量(20mg·kg^-1·d^-1)紫蓝素对大鼠连续灌胃给药6个月,观察大鼠一般状况、体质量、摄食量、饮水量、血液学、血液生化学、脏器系数及组织病理学变化。结果紫蓝素大、中、小剂量对大鼠一般状况、摄食量、饮水量和脏器系数均无明显影响;中剂量可引起大鼠中性粒细胞增多、淋巴细胞减少;大剂量对大鼠体质量有一定的抑制作用,可引起大鼠中性粒细胞增多,淋巴细胞、红细胞、血红蛋白、嗜酸性粒细胞减少,可引起大鼠总蛋白(TP)、肌酐(Cr)、肌酸磷酸激酶(CKP)含量降低,停药4周后均可恢复正常;大、中、小剂量组均未见药物所致毒性病理改变,亦未见药物引起的延迟性毒性反应。结论紫蓝素20mg·kg^-1为大鼠无毒性反应剂量。
Objective To observe oral toxicity of zilanine in rats and to evaluate its safety.Methods One hundred and sixty rats were randomly divided into 4 groups:control group,low,middle and high dose groups of zilanine.The rats were orally administrated with zilanine of 20,200 and 2000 mg·kg^-1·d^-1 for six months,respectively.The general condition,body weight,food consumption,water consumption,hematology,blood biochemistry test,organ coefficients and histopathological changes of all the rats were observed.Results There was no obvious effect on the general condition,food consumption,water consumption,organ coefficients in all the rats treated with zilanine.The middle dose zilanine caused an increase of neutrophils and a decrease of the number of lymphocytes.Rat body weight of high dose group was significantly lower than the control group.High dose of zilanine caused the increase of neutrophils,and the number of lymphocytes,the erythrocyte,hemoglobin,and eosinophil.The total protein(TP),creatinine(Cr),and creatine phosphokinase(CKP)decreased in rats.All of these parameters restored to baseline level after 4 weeks.No toxic pathological changes were observed in the high,middle and low dose groups,and no delayed toxic reactions were observed after 4 weeks of drug withdrawal.Conclusion The dose of 20 mg·kg^-1·d^-1 of zilanine shows non-toxic response at this study condition.
作者
郏自明
谢运昌
樊柏林
JIA Ziming;XIE Yunchang;FAN Bolin(Hubei Provincial Key Laboratory of Applied Toxicology,Hubei Provincial Academy of Preventive Medicine,Wuhan 430075,China;Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization,Guangxi Institute of Botany,Chinese Academy of Sciences,Guilin 541006,China)
出处
《医药导报》
CAS
北大核心
2019年第9期1134-1141,共8页
Herald of Medicine
基金
重大新药创制项目(2017ZX09301060-014)
关键词
紫蓝素
经口给药
毒性
长期
Zilanine
Oral administration
Toxicity,long term
