基于肠道菌群与代谢组学探讨补肾通腑方对AD小鼠神经炎症的影响  

Effect of Bushen Tongfu decoction on neuroinflammation in AD mice based on intestinal flora and metabolomics

作　　者：张杰[1] 王旭 宋晓雨 李思敏 段建平 许玉珉 赵敏[1] ZHANG Jie;WANG Xu;SONG Xiao-yu;LI Si-min;DUAN Jian-ping;XU Yun-min;ZHAO Min(Encephalopathy Center,the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450008,China;the First Clinical Medical College,Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学第一附属医院脑病中心,河南郑州450008 [2]河南中医药大学第一临床医学院,河南郑州450046

出　　处：《中国药理学通报》2024年第7期1258-1266,共9页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81904264)。

摘　　要：目的观察补肾通腑方对APP/PS1小鼠空间学习记忆能力的影响,探讨其可能的作用机制。方法APP/PS1小鼠给予补肾通腑方灌胃治疗8周后,采用Morris水迷宫法观察小鼠学习记忆能力变化;16S rDNA高通量测序和液相色谱-串联质谱(LC-MS/MS)方法检测小鼠肠道菌群及肠道代谢物的变化。结果与模型组比较,补肾通腑方能够明显缩短小鼠逃避潜伏期,减少游泳路程,增加跨越平台次数(P<0.01)。16S rDNA结果显示,补肾通腑方可以增加有益菌厚壁菌门Firmicutes丰度,降低有害菌拟杆菌门Bacteroidota的丰度。LC-MS/MS结果显示,共鉴定出25个差异代谢产物,主要涉及鞘脂代谢、赖氨酸代谢、酪氨酸代谢等代谢通路。KEGG富集分析显示,补肾通腑方主要通过NF-κB、Apelin等炎症相关信号通路发挥治疗作用。结论补肾通腑方改善APP/PS1小鼠学习记忆能力,可能与改善肠道菌群组成,影响鞘脂代谢、赖氨酸代谢、酪氨酸等的代谢,调控NF-κB、Apelin等炎症相关信号通路有关。Aim To explore the mechanism of Bushen Tongfu decoction(BSTF)improving the learning and memory ability of APP/PS1 mice.Methods The APP/PS1 mice were administered by BSTF for eight weeks.The spatial learning and memory ability of all mice were detected by Morris water maze.The changes in the intestinal microbiota and gut metabolites of mice were detected by 16S rDNA and LC-MS/MS technology.Results Compared with the model group,the escape latency and swimming path in BSTF-H,BSTF-M and BSTF-L groups were shortened and the times of target crossings after removing the platform increased significantly(P<0.01).The 16S rDNA results showed that BSTF could increase the abundance of beneficial bacteria of Firmicutes and reduce the abundance of harmful bacteria of Bacteroidota in APP/PS1 mice.A total of 25 differential metabolites were identified by LC-MS/MS,including sphingolipid metabolism,lysine metabolism and tyrosine metabolism.KEGG enrichment analysis showed that the therapeutic effect of BSTF was mainly through inflammation-related signaling pathways such as NF-κB pathways and Apelin pathways.Conclusions The mechanism of BSTF improving the learning and memory ability of APP/PS1 mice may be related to the improvement of intestinal flora composition,the effect of sphingolipid metabolism,lysine metabolism and tyrosine metabolism and the regulation of inflammation-related signaling pathways such as NF-κB and Apelin pathways.

关 键 词：阿尔茨海默病 补肾通腑方 学习记忆能力 肠道菌群 非靶代谢组学 神经炎症 

分 类 号：R-332[医药卫生] R289.5R322.45R338.64R364.5R745.7