王焕君 马致洁 董捷鸣 吴昊 于小红 段晓颖

摘要 目的：分析雷公藤配伍甘草减毒大鼠体内尿液中的小分子代谢物以及相应生物代谢通路。方法：选取30只SD大鼠正常饲养5 d，随机分为3组，即空白对照组、雷公藤组、雷公藤配伍甘草组，每组10只。应用HPLC-MS/MS-IT-TOF检测各组大鼠的尿液样本，并且按照偏最小二乘法-判别分析（PLS-DA）多元统计学方法以筛选并鉴定潜在的生物标志物;在此基础上推测其可能影响到的生物代谢通路。结果：大鼠尿液代谢组学分析结果显示，雷公藤配伍甘草组、雷公藤组和空百对照组分别聚集在不同的象限区域内;共鉴定出14个潜在的生物标志物，并且推测出嘌呤代谢和硒氨基酸代谢最具显著影响。结论：雷公藤配伍甘草减毒的机制复杂，其中可能通过调控嘌呤代谢和硒氨基酸代谢通路而实现。

关键词  雷公藤;甘草;配伍减毒;尿液;代谢组学;生物标志物;代谢通路;中药

Analysis of Toxicity Reduction on Tripterygium Wilfordii Combined with Radix Glycyrrhizae by Using Metabolomics of Rat Urine

WANG Huanjun¹，MA Zhijie²，DONG Jieming²，WU Hao²，YU Xiaohong²，DUAN Xiaoying³

（1 Henan University of Chinese Medicine，Zhengzhou 450000，China; 2 Department of Chinese Pharmacy，Beijing Friendship Hospital Affiliated to Capital Medical University，Beijing 100050，China; 3 The First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450008，China）

Abstract Objective：To analyze the changes of small molecular metabolites in urine of rats administrated by tripterygium wilfordii combined with Radix Glycyrrhizae，and the involved metabolic pathways by metabolomics.Methods：On the basis of the previous experiment，the rats were given different experimental intervention，specifically divided into tripterygium wilfordii group，tripterygium wilfordii combined with Radix Glycyrrhizae group and blank control group; HPLC-MS/MS-IT-TOF was used to detect urine samples of rats in each group，and PLS-DA multivariate statistical method was used to screen and identify potential biomarkers.On this basis，it is speculated that it may affect the biological metabolic pathways.Results：The results of urine metabolomics analysis showed that the groups were clustered in different quadrants.We together identified 14 potential biomarkers and speculated that purine metabolism and selenoamino acid metabolism had the most significant effects.Conclusion：The mechanism of tripterygium wilfordii combined with Radix Glycyrrhizae is complex，which may be achieved by regulating purine metabolism and selenoamino acid metabolism pathway.

Keywords Tripterygium wilfordii; Radix glycyrrhiza; Compatibility toxin reduction; Urine; Metabolomics; Biomarkers; Metabolic pathway; Chinese medicine

中图分类号：R282;R285 文献标识码：A doi：10.3969/j.issn.1673-7202.2020.08.003〖HK〗

雷公藤载于《神农本草经》，其性凉、味苦、有大毒、归肝肾经，具有抗炎[1]、抗肿瘤[2]、祛风除湿、舒经活络、消肿止痛、杀虫解毒的功效。在临床上，雷公藤可用于类风湿性关节炎等自身免疫性疾病的治疗，可发挥独特的治疗效果[3-5]。然而，伴随雷公藤发生的严重不良反应也是不可轻视的[6]，使其成为了近来出现中毒事件最多的中草药之一，尤其是雷公藤导致的肝毒性更是居单味药材肝损伤之首[7-8]。因此，针对于雷公藤的減毒存效研究是当前研究的重中之重。……