【摘要】 基于非靶向代谢组学技术，分析腹腔注射苦参碱前后昆明小鼠粪便和血浆代谢物的差异，并通过与此前16S rDNA测序结果联合分析探究苦参碱发挥药理作用的可能机理。将20只昆明小鼠随机分为2组，分别是苦参碱处理组（MT）和生理盐水处理组（NC）。苦参碱处理组每天腹腔注射40 mg·kg^-1的苦参碱，连续给药5 d,每天给药2次。生理盐水处理组按照同样方式和体积腹腔注射生理盐水。给药第6天，分别收集各组小鼠的粪便和血浆，进行非靶向代谢组学检测，并与苦参碱处理组肠道菌群的16S rDNA测序结果进行联合分析。苦参碱处理组的粪便及血浆中均存在显著差异代谢物，粪便中共鉴定出97种，血浆中有44种。聚类分析显示，粪便中苦参碱组有35种代谢物上调，104种代谢物下调；血浆中苦参碱组有20种代谢物上调，35种代谢物下调。KEGG通路分析显示粪便及血浆差异代谢物被映射到Protein digestion and absorption等代谢途径。与16S rDNA测序分析得到的显著差异菌种嗜酸乳杆菌关联分析，结果表明粪便及血浆代谢物与嗜酸乳杆菌存在相关性。苦参碱可调节昆明小鼠的体内代谢，在粪便和血浆中均存在显著差异代谢物。这些差异代谢物及与菌群之间的互作可能是其发挥药理作用的关键。更多还原

【Abstract】 The differences in the feces and plasma metabolites of Kunming mice before and after matrine administration were analyzed using the untargeted metabolomics method. The potential mechanisms of matrine on pharmacological actions were explored through the combined analysis of metabolomics and microbiome. Twenty Kunming mice were randomly divided into two groups, named matrine treatment group（MT） and normal saline treatment group（NC）. In the MT, 40 mg·kg^-1 of matrine was injected intraperitoneally to mice twice a day for 5 days. In the NC, saline was injected intraperitoneally with the same volume and method. On the 6 th day of administration, the feces and plasma of each group of mice were collected for the untargeted metabolomics analysis and the 16 S rDNA sequencing results obtained in the preliminary study were co-analyzed. The significant differential metabolites were obtained both in feces and plasma in matrine treatment group, and 97 metabolites in feces. while 44 in plasma. Cluster analysis showed that in matrine treatment group, 35 metabolites were up-regulated and 104 metabolites were down-regulated in feces, while 20 metabolites were up-regulated and 35 metabolites were down-regulated in plasma. KEGG analysis showed that the differential metabolites were mapped to metabolic pathways such as protein digestion and absorption. Moreover, there was a correlation between fecal and plasma different metabolites and Lactobacillus acidophilus obtained by 16 S rDNA sequencing. Matrine regulated the metabolism in Kunming mice, and differential metabolites were obtained both in feces and plasma. These differential metabolites and their interactions with the microflora might be the key to the pharmacological action.更多还原