基于粪便代谢组学的不同蒸晒程度何首乌改善阿尔茨海默病认知障碍的实验研究  

Experimental study on improvement of cognitive impairment in Alzheimer′s disease by different degrees of steaming and sunning of Polygoni Multiflori Radix based on fecal metabolomics

作　　者：周观琳 李绍燕 罗喜 陈泓 池鑫宇 刘舒凌 杨柯 曾春晖 ZHOU Guan-lin;LI Shao-yan;LUO Xi;CHEN Hong;CHI Xin-yu;LIU Shu-ling;YANG Ke;ZENG Chun-hui(College of Pharmacy,Guangxi University of Chinese Medicine,Nanning 530000,China)

机构地区：[1]广西中医药大学药学院,南宁530000

出　　处：《中国中药杂志》2024年第8期2147-2157,共11页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82060718);广西研究生教育创新计划项目(YCSW2022358);国家中医药管理局“中药炮制传承技术传承基地”资助项目(桂中医药发[2022]9号);广西中医药大学桂派杏林拔尖人才资助项目(桂中医大党[2022]23号);广西中医药大学桂派中医药传承创新团队项目(2022B005);广西一流学科建设开放项目(2019XK079)。

摘　　要：通过粪便代谢组学方法研究何首乌改善阿尔茨海默病(Alzheimer′s disease,AD)认知障碍的作用机制,并比较不同蒸晒程度何首乌在改善AD模型小鼠认知功能上的作用差异,探讨其炮制原理。选取48只5月龄APP/PS1小鼠随机分为模型组、阳性组、生品组、三蒸三晒组、六蒸六晒组、九蒸九晒组,另取7只同窝阴性对照小鼠作为空白组。灌胃给药150 d后,采用巴恩斯迷宫和避暗实验评估各组小鼠的学习记忆能力,并采集粪便样本进行广泛靶向代谢组学检测,结合主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA)等多元统计方法对小鼠粪便中的代谢物进行分析。通过对比模型组和不同炮制品组的行为学结果显示,六蒸六晒组在巴恩斯迷宫定位航行测试中潜伏期显著缩短(P<0.05),空间探索实验中错误次数显著减少(P<0.05);避暗实验中第一次进入暗箱的潜伏期显著延长(P<0.05),其综合改善AD模型小鼠的学习记忆能力最佳。代谢组学结果显示,与模型组相比,筛选出其他各组差异代谢物的数量排列顺序:六蒸六晒组>九蒸九晒组>生品组>三蒸三晒组,分别包含146、120、95和81种潜在生物标志物。其中,与AD疾病相关的差异代谢物共有16种。基于炮制程度的进一步比较,发现六蒸六晒何首乌组在总代谢通路的调节数量最多,主要回调戊糖和葡萄糖醛酸相互转化和调节氨基酸合成代谢等途径。综上,何首乌经炮制后改善APP/PS1小鼠的学习记忆能力的作用机制可能与改善氨基酸代谢以及提高机体能量代谢水平有关,以六蒸六晒炮制程度最佳。The fecal metabolomics method was employed to investigate the cognitive improvement mechanism of Polygoni Multiflori Radix in Alzheimer′s disease(AD)and examine the effects of different degrees of steaming and sunning on cognitive function in AD model mice.Additionally,the processing principle of Polygoni Multiflori Radix was discussed.Forty-eight 5-month-old APP/PS1 mice were randomly assigned to the following groups:model group,positive group,raw product group,three-steaming and three-sunning product group,six-steaming and six-sunning product group,and nine-steaming and nine-sunning product group.Seven negative control mice from the same litter were included as the blank group.After 150 days of intragastric administration,the learning and memory abilities of mice in each group were assessed by using the Barnes maze and dark avoidance tests.Fecal samples were collected for extensive targeted metabolomics testing.Principal component analysis(PCA),orthogonal partial least squares discriminant analysis(OPLS-DA),and other multivariate statistical methods were utilized to analyze metabolites in mouse feces.Comparison of behavioral results between the model group and different product groups demonstrated that the six-steaming and six-sunning product group exhibited significantly reduced latency in the Barnes maze positioning and navigation test(P<0.05),as well as a notable decrease in the number of errors in the space exploration experiment(P<0.05).Moreover,the latency of mice entering the dark box for the first time in the dark avoidance experiment was significantly prolonged(P<0.05),indicating the best overall improvement in the learning and memory ability of AD model mice.Metabolomics results revealed that compared with the model group,the differential metabolites in other groups in descending order were as follows:six-steaming and six-sunning product group>nine-steaming and nine-sunning product group>raw product group>three-steaming and three-sunning product group,encompassing 146,120,95,and 81 potential biomark

关 键 词：何首乌 蒸晒炮制 粪便代谢组学 阿尔茨海默病 氨基酸代谢 能量代谢 

分 类 号：R285.5[医药卫生—中药学]