苯溴马隆对高尿酸血症模型大鼠脂质代谢的影响

Effects of Benzbromaroneon on Lipid Metabolism in Hyperuricemic Rats

关键词:  苯溴马隆  高尿酸血症  脂质组学  超高效液相色谱-四极杆飞行时间质谱(UPLC-Q-TOF/MS)  甘油磷脂

Key words:  benzbromarone  hyperuricemia  lipidomics  UPLC-Q-TOF/MS  glycerophospholipid

摘要:

目的 基于脂质组学方法研究苯溴马隆治疗高尿酸血症（hyperuricemia，HUA）大鼠的作用机制，并揭示尿酸水平增高与脂质代谢异常的内在相关性。方法 利用超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF/MS）技术，结合主成分分析（PCA）和偏最小二乘法判别分析（OPLS-DA）研究正常组、模型组和苯溴马隆组的大鼠血清中内源性脂质代谢物的变化，寻找潜在生物标记物，分析相关代谢通路，绘制代谢网络机制图。结果 脂质组学分析发现，苯溴马隆可使HUA大鼠体内水平异常的20个差异代谢物回调到正常水平；相关代谢通路分析发现，苯溴马隆影响果糖诱导HUA大鼠血清中的脂质水平，主要与甘油磷脂代谢通路相关。结论 苯溴马隆对HUA的治疗可能与改善体内甘油磷脂代谢通路异常密切相关。

Abstract:

OBJECTIVE To investigate the pharmacologic mechanisms of benzbromarone in the treatment of hyperuricemia (HUA) rats by means of lipidomics and to reveal the correlation between the high uric acid level and abnormal lipid metabolism. METHODS ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC/TOF-MS) combined with pattern recognition approaches (PCA and OPLS-DA) were used to determine differentiating metabolites, search for potential biomarkers, analyze the metabolic pathways, and map the metabolic network in serum of normal group, model group and benzbromarone group. RESULTS Lipidomics analysis found that benzbromarone could make 20 of abnormal metabolites in HUA rats revert to normal levels. The related metabolic pathway analysis found that benzbromarone influenced fructose-induced HUA, it mainly associated with glycerophospholipid metabolism pathways. CONCLUSION The result provides that the mechanism of benzbromarone in the treatment of HUA maybe have close correlation with glycerophospholipid metabolic disorders.