基于脑代谢组学研究羚珠散联合对乙酰基氨基酚对发热幼龄大鼠的解热作用

  目的  探讨中成药羚珠散(Ling-Zhu-San, LZS)和西药对乙酰氨基酚(Acetaminophen, APAP)对幼龄大鼠的解热作用及其代谢影响。  方法  采用气相色谱-质谱联用平台、多变量统计技术和通路分析等方法,通过系统的代谢组学分析,确认治疗前后大鼠脑组织中代谢物水平变化;通过体温试验和酶联免疫吸附实验(ELISA)考察大鼠体温变化及白细胞介素-1β (Interleukin-1β,IL-1β)和前列腺素E₂ (Prostaglandin E₂, PGE₂)的含量。  结果  大鼠脑内与TCA循环、色氨酸代谢、谷氨酸代谢和花生酸代谢相关的16种显著改变的代谢物(P < 0.05, FC>1.5)被认为是潜在的发热生物标志物,而联合用药后这些代谢物的浓度均基本恢复至正常水平。羚珠散和对乙酰氨基酚联用较单药解热效果最佳。  结论  羚珠散和对乙酰氨基酚联合用药对幼龄大鼠的解热作用可能与其改善脑内代谢紊乱相关。 

Brain Metabolomics Reveals the Antipyretic Effects of Combined Use of Ling-Zhu-San and Acetaminophen in Young Rats Using Gas Chromatography-Mass Spectrometry

  OBJECTIVE  To investigate the antipyretic and metabolic effects of Ling-Zhu-San (LZS) and Acetaminophen (APAP) on young rats.  METHODS  The changes of metabolite levels in rat brain were confirmed by GC-MS platform, multivariate statistical technique and pathway analysis. The changes of temperature and the contents of IL-1β and PGE2 in rats were investigated by temperature test and enzyme-linked immunosorbent assay.  RESULTS  16 metabolites associated with TCA cycle, tryptophan metabolism, glutamate metabolism and arachidonic acid metabolism (P < 0.05, FC>1.5). These metabolites were considered as potential biomarkers of fever. And the concentration of these metabolites basically recovered to normal levels after combination therapy. LZS combined with APAP had the best antipyretic effect.  CONCLUSION  These results suggest that the antipyretic effect of LZS combined with APAP on young rats may be related to its improvement of brain metabolic disorders.