甘草干预雷公藤内酯酮的代谢组学分析  

Effect of Glycyrrhizae Radix et Rhizoma on Metabonomics of Triptonide

作　　者：刘建群[1] 王卓[2,3] 徐金娣[3] 张国华[1] 辛贵忠[2] 李松林[3] 刘丽芳[2] 

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室,南昌330004 [2]中国药科大学天然药物活性组分与药效国家重点实验室,南京210009 [3]江苏省中医药研究院,南京210028

出　　处：《中国实验方剂学杂志》2016年第19期70-75,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81160541);江西省卫生厅中医药科研项目(2011A143)

摘　　要：目的:研究甘草对雷公藤内酯酮代谢组学的影响,发现雷公藤内酯酮毒性生物标记物及受甘草回调的表征雷公藤内酯酮毒性的减毒生物标记物,探讨雷公藤内酯酮毒性及甘草对雷公藤内酯酮的减毒作用机制。方法:将30只SD大鼠随机等分为空白组、雷公藤内酯酮单独给药组、雷公藤内酯酮与甘草联用组,雷公藤内酯酮给药剂量0.7 mg·kg^(-1),联用组在腹腔注射给予雷公藤内酯酮注射液前2 h按剂量3 m L·kg^(-1)灌胃给予甘草溶液,连续给药7 d。收集各组尿液进行UPLC-Q-TOFMS测定,采用主成分分析(PCA)和正交偏最小二乘法-判别分析(OPLS-DA)对样品数据进行对比分析。结果:发现雷公藤内酯酮毒性生物标记物7个,4个生物标记物鉴定为泛酸、犬尿喹啉酸、色氨酸和粪卟啉,另3个生物标记物结构待定。其中受甘草回调的减毒生物标记物4个,已确认结构的为色氨酸,其余3个结构待定。结论:雷公藤内酯酮的毒性机制可能与其干扰了机体的能量代谢、色氨酸代谢、卟啉代谢等途径有关,甘草的减毒作用与其对这些代谢途径的回调有关。Objective： To investigate effect of Glycyrrhizae Radix et Rhizoma on metabonomics of triptonide,find toxicity biomarkers and attenuation biomarkers induced by Glycyrrhizae Radix et Rhizoma and disclose toxicity and attenuation mechanism of Glycyrrhizae Radix et Rhizoma on triptonide. Method： SD rats were randomly divided into three groups of the control group,the triptonide group（ dose of 0. 7 mg·kg-1） and the triptonide（ dose of 0. 7 mg·kg-1） ＋ Glycyrrhizae Radix et Rhizoma（ dose of 3 m L·kg-1） group. All drug treatments were administered daily for consecutive 7 days. All urine samples were determined by UPLC-Q-TOFMS. These obtained data were analyzed by principal component analysis（ PCA） and orthogonal partial leastsquares-discriminant analysis（ OPLS-DA）. Result： Seven biomarkers related to toxicity of triptonide were found,four of them were identified as pantothenic acid,kynurenic acid,tryptophan and coproporphyrin,respectively.Four attenuation biomarkers were identified,one of them was tryptophan,but these remaining three biomarkers were unknown. Conclusion： These toxicity biomarkers and attenuation biomarkers are identified for the first time.It is indicated that toxicity of triptonide interfered with the energy,tryptophan and porphyrin metabolisms in body,recover of these metabolisms induced by Glycyrrhizae Radix et Rhizoma may be a physiological attenuation mechanism of Glycyrrhizae Radix et Rhizoma on triptonide.

关 键 词：甘草 雷公藤内酯酮 代谢组学 减毒生物标记物 色氨酸 粪卟啉 泛酸 

分 类 号：R969.1[医药卫生—药理学] R945[医药卫生—药学]