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运用代谢组学及生物效应网络方法研究槲皮素生物效应的机制。采用高效液相色谱-质谱(HPLC-MS)联用技术测定空白组与槲皮素给药组大鼠血清,质谱数据采用MATLAB软件处理,利用偏最小二乘辨别法分析空白组、槲皮素给药组之间的代谢差异,并通过变量重要性投影选取潜在的生物标志物,结合质谱信息和数据库检索对潜在的生物标志物进行鉴定,确定了4个化合物的结构、代谢途径,以及相关的酶和作用靶点,分别为维生素A酸及视黄醛酸受体(RARβ)、花生四烯酸和COX-2同工酶、3,5-二碘酪氨酸及甲状腺过氧化物酶(TPO)、尿苷二磷酸葡萄糖和磷酸二酯酶(PDEs)。通过生物效应网络并结合相关文献证明槲皮素可使维生素A酸对视黄醛酸受体(RARβ)的诱导能力增强、活化甲状腺过氧化物酶(TPO)、还可作为COX-2同工酶和磷酸二酯酶(PDEs)的抑制剂。该研究在生物分子网络调控的层面阐释了槲皮素的多种生物效应,说明代谢组学及生物效应网络方法能用于槲皮素生物效应机制的研究,为进一步揭示药物作用机制提供了新方法。
Study on the mechanism of quercetin biological effects using metabolomics and bioeffect networks. The serum and mass spectrometry data of rats in blank group and quercetin administration group were determined by HPLC-MS. The data were processed by MATLAB software. The data of blank control group, quercetin The metabolic differences between the two groups were also investigated. Potential biomarkers were selected by variable importance projection, and the potential biomarkers were identified by mass spectrometry and database search. The structures, metabolic pathways and the correlations of four compounds were identified Of the enzyme and target points, respectively, retinoic acid and retinoic acid receptor (RARβ), arachidonic acid and COX-2 isoenzyme, 3,5-diiodotyrosine and thyroid peroxidase (TPO), uridine diphosphate and phosphodiesterases (PDEs). Quercetin can enhance the ability of retinoic acid to induce retinaldehyde receptor (RARβ), activate thyroid peroxidase (TPO), and also act as COX-2 co-worker Inhibitors of enzymes and phosphodiesterases (PDEs). This study elucidated the various biological effects of quercetin at the level of regulation of biomolecular networks, indicating that metabolomics and bioeffective networks could be used to study the biological effects of quercetin, providing new insights into the mechanism of action of quercetin method.