高尿酸血症认知功能障碍模型大鼠皮层和海马的代谢组学研究

Metabolomic analysis of cerebral cortex and hippocampus in rats with hyperuricemia-induced cognitive dysfunction

目的基于核磁共振氢谱(1H-NMR)代谢组学方法研究高尿酸血症诱发大鼠认知功能障碍模型的皮层和海马的内源性差异代谢物变化。方法采用含2%尿酸和2%氧嗪酸钾的高尿酸复合饲料饲喂大鼠12周,Morris水迷宫测定大鼠认知功能,并利用1H-NMR分析大鼠皮层和海马中的差异代谢物。结果高尿酸血症大鼠显示较长的逃逸潜伏期,表现出认知功能障碍;且大鼠的皮层和海马中分别筛选出27和18种差异代谢物,其中共有6种差异代谢物。γ-氨基丁酸、谷氨酸、谷氨酰胺、乳酸、甘露醇、牛磺酸和谷胱甘肽均有显著变化,可能作为高尿酸血症认知功能障碍的特征生物标志物,与学习、记忆功能损伤的发生和发展密切相关。结论高尿酸饮食可干扰机体的正常代谢,其诱发认知功能障碍机制可能与能量代谢的糖酵解和三羧酸循环、氨基酸代谢、氧化应激、神经递质转化以及细胞膜功能的紊乱等有关。

Aim To study the changes in endogenous differential metabolites of cerebral cortex and hippocampus extracts from cognitive dysfunction rats induced by hyperuricemia using 1H nuclear magnetic resonance(1H-NMR)based metabolomics assay.Methods The rats were treated with 2%uric acid and 2%oxonic acid diet for 12 weeks,and assessed for spatial learning ability using Morris water maze.Metabolic profiles of the cerebral cortex and hippocampus were assessed using 1H-NMR.Results Compared with control group,the hyperuricemia rats showed significantly increased escape latency.All together 27 and 18 differential metabolites were identified respectively in cerebral cortex and hippocampus using 1H-NMR based metabolomics assay,and 6 same differential metabolites were identified among them.The levels ofγ-aminobutyrate,glutamate,glutamine,lactate,mannitol,taurine and glutathione have significant changes.These differential metabolites may be characteristic biomarkers of hyperuricemia-induced cognitive dysfunction,correlated with the progression of cognitive impairment.Conclusions High uric acid diet can cause disturbance in normal metabolisms and its mechanism is possibly related with disorders in glycolysis,tricarboxylic acid cycle,amino acid metabolism,oxidative stress,neurotransmitter transformation and cell membrane function.