Zhang Shuli, Zhuang Jingcong, Yue Guijuan, Wang Yiping, Liu Mingyu, Zhang Bing, Du Zhenxia, Ma Qun
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
College of Science, Beijing University of Chemical Technology, Beijing 100029, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Aug 15;1060:407-415. doi: 10.1016/j.jchromb.2017.06.037. Epub 2017 Jun 20.
Hyperuricemia caused by purine metabolic abnormalities is reported to have close correlation with lipid metabolic disorders. Ginkgo folium, a frequently-used lipid-lowering medicine, has significant anti-hyperuricemia effects. However, it is poorly known about the interaction between lowering uric acid and regulation of lipid metabolic disorders. In this study, hyperuricemic rat model was induced by orally administration with fructose. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with pattern recognition approaches were used to determine different lipid metabolites in serum of control group, model group, and different doses of ginkgo folium groups. Principal component analysis (PCA) was applied to analyze the MS data to assess the establishment of model, partial least squares-discriminate analysis (PLS-DA) and independent samples T-test were performed to indicate the differences between different groups of rats and to find biomarkers. Metabolomics pathway analysis (MetPA) was introduced to reveal the pharmacologic mechanisms of ginkgo folium. 19 potential biomarkers associated with hyperuricemia were found. After intervened by ginkgo folium, these biomarkers were returning to normal level. Among these biomarkers, 13 lipid biomarkers were significantly reversed. Ginkgo filum can lower uric acid via adjusting back the level of PCs and LPCs, which suggested that its treatment mechanisms may be related to reducing the activity of PLA2. In sum, the lipidomics analysis in the system level have enhanced our understanding to pathogenesis of hyperuricemia and the results suggested that ginkgo folium could alleviate the abnormal metabolic status of hyperuricemia. These results demonstrated a new mechanism for lowering uric acid, which was helpful to the early treatment for hyperuricemia.
据报道，由嘌呤代谢异常引起的高尿酸血症与脂质代谢紊乱密切相关。银杏叶是一种常用的降脂药物，具有显著的抗高尿酸血症作用。然而，关于降尿酸与脂质代谢紊乱调节之间的相互作用却鲜为人知。在本研究中，通过口服给予果糖诱导建立高尿酸血症大鼠模型。采用超高效液相色谱-四极杆-飞行时间质谱联用（UPLC-Q-TOF/MS）结合模式识别方法，测定对照组、模型组和不同剂量银杏叶组大鼠血清中的不同脂质代谢物。应用主成分分析（PCA）对质谱数据进行分析以评估模型的建立，进行偏最小二乘判别分析（PLS-DA）和独立样本T检验以表明不同组大鼠之间的差异并寻找生物标志物。引入代谢组学通路分析（MetPA）以揭示银杏叶的药理机制。发现了19种与高尿酸血症相关的潜在生物标志物。经银杏叶干预后，这些生物标志物恢复到正常水平。其中，13种脂质生物标志物有显著逆转。银杏叶可通过调节PCs和LPCs水平来降低尿酸，这表明其治疗机制可能与降低PLA2活性有关。总之，系统水平的脂质组学分析加深了我们对高尿酸血症发病机制的理解，结果表明银杏叶可缓解高尿酸血症的异常代谢状态。这些结果证明了一种新的降尿酸机制，有助于高尿酸血症的早期治疗。
