基于尿液代谢组学的附子配伍甘草减毒作用研究

Urine Metabolomics Analysis of Toxicity Attenuation Effects of Fuzi Compatibility with Gancao

目的:利用代谢组学方法,基于附子毒性生物标记物配伍甘草前后的轨迹变化规律,阐释附子配伍甘草的减毒作用机制。方法:采用UPLC-HDMS对连续给药6个月的附子组、附子-甘草组和空白对照组大鼠尿液代谢轮廓进行分析,结合组织病理学观察结果,分析鉴定与附子毒性相关的生物标记物及相关代谢通路,并对附子与甘草配伍前后大鼠体内毒性生物标记物表达水平进行比较。结果:确定了12个与附子毒性相关的生物标记物和与之相关的6条代谢通路,附子配伍甘草后对其中10个毒性生物标记物具有较好的回调作用。结论:附子与甘草配伍可通过调节戊糖、葡萄糖醛酸转换,淀粉和蔗糖代谢,丙氨酸、天冬氨酸和谷氨酸代谢等代谢通路;有效降低附子的毒性,从代谢产物角度揭示中药配伍减毒的科学性,为附子的临床用药安全提供参考。

Objective:Using metabolomics method to explore the toxicity-attenuating mechanism of Fuzi compatibility with Gancao based on the trajectory changes of Fuzi toxic biomarkers before and after compatibility. Methods:The UPLC-HDMS was used to analyze the urine metabolic profile of the Fuzi group,Fuzi-Gancao group and control group for 6 months,and the histopathological observations were used to identify the biomarkers associated with Fuzi toxicity.The related metabolic pathways were compared and the expression levels of toxic biomarkers in rats before and after the combination of Fuzi and Gancao were also compared. Results:Twelve biomarkers related to Fuzi toxicity and 6 metabolic pathways were identified.Fuzi compatibility with Gancao had a good callback effect on 10 toxic biomarkers. Conclusion:Fuzi compatibility with Gancao can effectively reduce the toxicity of Fuzi by regulating the metabolism of pentose,glucuronic acid,metabolism of starch and sucrose,alanine,aspartic acid and glutamic acid.It reveal the science of compatibility toxicity-attenuation from the perspective of metabolites,and provide reference for the clinical safety of Fuzi.