Xanifolia Y的急性毒性与溶血性研究

Study on the acute toxicity and hemolytic property of Xanifolia Y

目的对来自植物药文冠果中的主成分Xanifolia Y的毒性、溶血性进行研究,为后期新药开发奠定基础。方法毒性试验选用阶梯法和Bliss法来测定半数致死量(LD50)。阶梯法选用SPF级健康雌性昆明种小鼠13只,以1 mg·kg^-1为起始剂量,相邻剂量比为1∶0.7,给药方式为尾静脉注射,遵循《化学药物急性毒性试验技术指导原则》进行试验。Bliss法选用SPF级健康雌性昆明种小鼠42只,随机分为7组,每组6只,设定6个剂量组(4.08、5.83、8.33、11.9、17、24.3 mg·kg^-1)和空白对照组,给药方式为尾静脉注射,给药一次后,连续观察14天,记录各组小鼠的存活情况,运用Bliss法计算LD50,检测存活小鼠的生理生化指标,对小鼠心脏、肝脏、脾脏、肾脏等主要脏器进行病理切片观察。溶血实验取SPF级健康雌性家兔,经动脉插管取血并制备2%血细胞悬浮液,设定10个剂量组(0.156、0.313、0.625、1.25、2.5、5、10、20、40、80 mg·L^-1),按照《中华人民共和国药典》(2015版)"溶血与凝聚检查法"指导通则进行溶血实验。结果Xanifolia Y静脉注射的LD50值为8.35 mg·kg^-1,组织切片和生化指标检测结果表明,Xanifolia Y能诱导肝窦充血与肾小管上皮细胞变性;能够诱导GOT和Cr异常升高。Xanifolia Y在0.63 mg·L^-1的浓度表现出较强的溶血性,其安全剂量应为0.31 mg·L^-1以下。结论Xanifolia Y的安全阈值较低,溶血活性极强,体内毒性主要表现为肝毒性与肾毒性。

Objective To research the acute toxicity and hemolytic property of Xanifolia Y,the principal component from husks of Xanthoceras sorbifolia Bunge,so as to lay a foundation for the later development.Methods Female mice were selected to conduct the up and down procedure and Bliss method to determine LD50.1 mg·kg^-1 as the starting dose for the up and down procedure and the adjacent dose ratio as 1∶0.7.The drug administration was i.v.and the test was conducted in accordance with the technical guidelines for acute toxicity test of chemical drugs.Bliss method were randomly divided into seven groups,including six dose groups(4.08,5.83,8.33,11.9,17,24.3 mg·kg^-1)and the control group.After intravenous injection,every group were continuous observation for 14 days,record the cumulative survival,food consumptions,weight,using the Bliss method to calculate LD50.After observation,pathological of organs and the expression of GOT,GPT and Cr would be tested.Female rabbits were used to the hemolysis experiment.All procedures were under the guidance of the rule for"hemolysis and coagulation test"in Chinese Pharmacopoeia,2015 edition.Results The LD50 of Xanifolia Y was 8.35 mg·kg^-1.The results of Elisa and H&E staining test were showed the toxicity of liver and kidney respectively.Xanifolia Y has shown strong hemolytic activity at 0.63 mg·L^-1 and its safe dosage should be less than 0.31 mg·L^-1.Conclusion Xanifolia Y has low safety dosage threshold,strong hemolytic activity and toxicity of liver and kidney.