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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 study the effects of licorice root on the metabolites of triptolide and find that the toxicity biomarkers of triptolide and triptolide-induced toxicity of triptolide are different from that of triptolide, Attenuated mechanism of triptolide. Methods: Thirty SD rats were randomly divided into blank group, triptolide alone group, triptolide and licorice combined group, triptolide dose 0.7 mg · kg -1, . The combination group was administered with licorice solution by intragastric administration of 3 m L · kg -1 2 h before intraperitoneal injection of triptolide for 7 days. The urine samples of each group were collected and analyzed by UPLC-Q-TOFMS. The principal component analysis (PCA) and orthogonal partial least square analysis (OPLS-DA) were used to analyze the sample data. Results: Seven bioartificial biomarkers of triptolide were found. The four biomarkers were identified as pantothenic acid, kynurenic acid, tryptophan and coproporphyrin, and the structures of the other three biomarkers to be determined. Among them, four attenuated biomarkers were readjusted by licorice, and the structure of tryptophan was confirmed. The remaining three structures to be determined. Conclusion: The toxicity mechanism of triptolide may be related to its interference with the body’s energy metabolism, tryptophan metabolism, metabolism of porphyria and other ways, licorice attenuated by their metabolic pathways and the callback.