四物汤对增龄过程中12月龄雄性小鼠调节作用的代谢组学研究

Metabolism of regulating effect of Siwu Decoction in the twelve month old male mice

目的:观察四物汤对增龄小鼠体内代谢标志物及代谢通路的影响,解析其多靶点调节作用,探寻四物汤干预增龄进程小鼠各阶段的生物学基础。方法:选用自然增龄小鼠,研究12月龄雄性小鼠脾组织代谢谱,经多元统计分析后,对比研究各对照组与四物汤给药4.68g/kg组小鼠脾组织代谢物的差异,确定增龄有关的生物标志物并分析代谢途径。结果:鉴定出牛磺酸、尿酸、前列腺素E1等24个生物标志物,四物汤给药4.68g/kg组对其中9个代谢标志物有明显调整趋势,进行MetPA分析发现其主要影响4条代谢途径。结论:四物汤给药4.68g/kg组对花生四烯酸、黄嘌呤、甘氨胆酸等标志物有明显调节作用,推测调节作用可能与增强抗氧化、调节免疫及清除体内氧自由基水平相关;并且该方通过影响牛磺酸和牛磺酸代谢、丙酮酸代谢、花生四烯酸代谢及嘌呤代谢等通路来干预增龄小鼠生长进程。

Objective： To observe the effect of Siwu Decoction on the metabolic markers and metabolic pathway in mice,and to explore the multi target regulation mechanism and the biological basis of Siwu Decoction intervention in aging process. Methods： Lultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry（UPLC-Q-TOF-MS） is a commonly used technique to characterize analytes in metabolomic studies. Thus,in this experiment,twelve aged male mice spleen tissue metabolism spectrum was obtained and measured with UPLC-TOF/MS technology,and the data was analyzed by principal components analysis（PCA）,and combined PLS-DA and Orthogonal partial least squares-discriminant analysis（OPLS-DA）. Results： It showed that 24 biomarkers were identified as main Metabolic markers,including Taurine,Uric acid and Prostaglandin E1. Compared with the model group,9 metabolic markers had a trend to regulate the growth of the aging process in 4. 68 g/kg Siwu Decoction. Besides,Siwu Decoction on some markers such as glycocholic acid,Docosahexaenoic acid,Arachidonic acid and Xanthine had an obviously callback effect. Through MetPA analysis,4 kinds of metabolic pathways were observed as major factors. Conclusion： Arachidonic acid,glycocholic acid,and other markers product a important bidirectional regulation. It may be associated with the aging process. It was further confirmed that the intervening effect might be associated with the enhancement of antioxidation,regulation of immune and scavenging of oxygen free radicals in vivo. In addition,the regulation mechanism of Siwu Decoction on metabolic disorder in the aging process was achieved by adjusting the taurine and hypotaurine metabolism,pyruvate metabolism,arachidonic acid metabolism and purine metabolism pathway.