钩藤散改善APP/PS1双转基因小鼠学习记忆功能的代谢组学研究

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。

The Metabolomic Study of Learning and Memory Function of APP/PS1 Double Transgenic Mice Improved by Gouteng San

ABSTRACT Objective: The non targeted high-throughput urine metabolomics technology was used to study the pathogenesis of APP/PS1 double transgenic mice and the mechanism of action of Gouteng san. Methods: 5-month-old APP/PS1 double transgenic mice were test with Morris water maze for spatial learning ability. Then we employed the non targeted high-throughput urine metabolomics technology to study the pathogenesis of APP/PS1 double transgenic mice based on the metabolic network. The focus investigation of the key pathways and the observation of the treatment by Morris water maze and metabolic level have been used after spatial learning ability damaged confirmed. Results: The comparison between APP/PS1 double transgenic mice and normal mice suggested that a significant longer was existed in former, which was call-back by Gouteng san. With the non targeted high-throughput urine metabolomics analysis and pathway focused analysis, we found certain signals from metabolic profiling, which was identified to be 6 biomarkers associated with learning and memory function by mass spectrometry analysis or authoritative database. Respectively, they were taurine, pteroylglutamic acid, neopterin, glutaurine, 2-oxoglutarate and dihydroneopterin. They were mainly related to taurine metabolism and folate metabolism and represented an effective callback. Conclusion: Gouteng san possess a favorable effect on learning and memory ability of APP/PS1 double transgenic mice, 6 biomarkers may be a potential target for the pathogenesis of APP/PSI double transgenic mice and provide ex- perimental basis for the study of Gouteng san.