目的:采用非靶向的高通量尿液代谢组学技术对钩藤散改善淀粉样前体蛋白/早老素蛋白1基因,即APP/PS1双转基因小鼠的作用机制进行研究。方法:5月龄APP/PSI小鼠采用Morris水迷宫实验检测双转基因小鼠的空间学习能力,在确定出现空间记忆能力功能损伤地条件下采用基于非靶向的尿液代谢组学技术研究APP/PSI小鼠的代谢网络,聚焦关键通路,同时观察钩藤散在水迷宫和代谢水平上的治疗作用。结果:Morris水迷宫对比发现APP/PSI小鼠的空间记忆能力明显长于同窝野生小鼠,给予钩藤散后呈现一定程度的回调趋势,经非靶向的代谢轮廓分析和核心代谢通路聚焦后,成功发现正常小鼠(同窝野生小鼠)和APP/PSI双转基因小鼠代谢轮廓间差异最大的信号,经质谱解析和权威数据库检索后鉴定6个与学习记忆相关的潜在生物标记物,分别是牛磺酸(taurine)、叶酸(pteroylglutamic acid)、新蝶呤(neopterin)、磺乙谷酰胺(glutaurine)、戊邻酮二酸盐(2-oxoglutarate)、二氢新蝶呤(dihydroneopterin),他们主要涉及牛磺酸代谢及叶酸代谢等,经钩藤散治疗后能有效回调。结论:钩藤散对APP/PSI双转基因小鼠的学习记忆能力具有一定治疗作用,本次发现的6个生物标记物可能是APP/PSI双转基因小鼠发病的潜在靶点,为钩藤散的相关药效学研究提供实验依据。 OBJECTIVE: To investigate the mechanism of Gouteng San improving amyloid precursor protein / presenilin 1 gene, namely APP / PS1 double transgenic mice, using non-targeted high-throughput urine metabolomics. Methods: Morris water maze test was used to detect the spatial learning ability of double transgenic mice at 5-month-old APP / PSI mice. Based on the non-targeted urine metabolomics study APP / PSI mice metabolic network, focusing on key pathways, while observing Uncaria scattered water maze and the therapeutic effect on the level of metabolism. Results: Compared with the wild-type mice, APP / PSI mice showed significantly greater spatial memory in the Morris water maze compared with those in the wild-type mice. After giving Gouteng San, there was a trend toward a certain degree of callback. After non-targeted metabolic profiling and focusing on the core metabolic pathway , The most significant difference between the metabolic profiles of normal mice (littermate mice) and APP / PSI double transgenic mice was successfully identified. Six potential biomarkers related to learning and memory were identified after mass spectrometry analysis and authoritative database search. Are respectively taurine, pteroylglutamic acid, neopterin, glutaurine, 2-oxoglutarate, dihydroneopterin, , They are mainly involved in taurine metabolism and folic acid metabolism, after the treatment of Uncaria can effectively callback. Conclusion: Gouteng San has a therapeutic effect on the learning and memory abilities of APP / PSI double transgenic mice. The 6 biomarkers found in this study may be potential targets of APP / PSI double transgenic mice, Related pharmacodynamics to provide experimental evidence.