柚皮苷改善东莨菪碱模型小鼠学习认知能力的血液代谢组学研究

Hematological metabonomics study of naringin improving learning cognitive ability of scopolamine model mice

目的:从代谢组学角度研究骨碎补总黄酮中柚皮苷对东莨菪碱致记忆损伤模型小鼠的学习记忆、认知能力的保护机制。方法:取3月龄雄性昆明种小鼠按体质量随机分为空白组、模型组和给药组。采用东莨菪碱构建记忆损伤模型,新物体识别实验和水迷宫实验检测小鼠学习记忆能力,然后对小鼠血液样品进行代谢物图谱及血液代谢物变化分析。结果:行为学实验结果显示,给药后小鼠的学习记忆能力较模型组明显改善。代谢组学研究结果显示,给药后小鼠血液的代谢轮廓都有显著的回调趋势,共鉴定出差异代谢物21个,其中L-乙酰肉碱、柠檬酸水平给药后显著上升,脯氨酸、色氨酸、溶血磷脂酰胆碱(14∶0)、溶血磷脂酰碱(15∶0)、脱氧胞苷、4-氨基苯酚水平给药后显著降低,涉及牛磺酸和亚牛磺酸代谢、色氨酸代谢、精氨酸和脯氨酸代谢、维生素B_(6)代谢、酪氨酸代谢、柠檬酸循环。结论:柚皮苷能够改善东莨菪碱模型小鼠学习记忆能力,其作用机制可能与改善能量代谢,减少β样淀粉蛋白(Aβ)产生,降低Tau蛋白过度磷酸化,促进神经突触可塑性,改善乙酰胆碱系统紊乱,抗氧化应激和抗细胞凋亡等作用有关。

Objective:To study the protective mechanism of naringin in total flavonoids of Rhizoma Drynariae on learning,memory and cognitive ability of scopolamine-induced memory damage model mice from the perspective of metabonomics.Methods:Three-month-old male Kunming mice were randomly divided into blank group,model group and treatment group according to their body weight.A model of memory damage was constructed using scopolamine.The effects of naringin on learning and memory ability in mice were observed by objectrecognition test and water maze test.Then mouse blood samples were detected for metabolite profiling analysis and the changes of blood metabolite analysis.Results:The behavioral experimental results showed that the learning and memory abilities of the mice after administration of the drug were significantly improved as compared with those in the model group.The metabolomics research results showed that the metabolic profiles of mouse blood showed a significant callback trend after administration of drug,and 21 differential metabolites were identified,of which,the levels of L-acetylcarnitine and citric acid significantly increased after administration,while the levels of proline,tryptophan,lysophosphatidyl choline(14∶0),lysophosphatidyl choline(15∶0),deoxycytidine and 4-aminophenol significantly decreased after administration,involving taurine and hypotaurine metabolism,tryptophan metabolism,arginine and proline metabolism,vitamin B;metabolism,tyrosine metabolism and citric acid cycle.Conclusion:Naringin can improve the learning and memory ability of scopolamine model mice.The protective effect of naringin may be related to improving energy metabolism,reducingβ-amyloid protein(Aβ)production,reducing Tau hyperphosphorylation,promoting synaptic plasticity,improving acetylcholine system disorders,anti-oxidative stress and anti-cells.