机构地区:[1]贵州中医药大学实验动物研究所,贵阳550025 [2]广州中医药大学东莞医院,东莞523000 [3]上海懿尚生物科技有限公司,上海201319
出 处:《实验动物与比较医学》2023年第3期253-261,共9页Laboratory Animal and Comparative Medicine
基 金:贵州省科技计划项目“贵州香猪疫病监测体系建立及主要疫病防控技术研究”(黔科合支撑〔2020〕1Y035)。
摘 要:目的基于液相色谱-串联质谱联用(liquid chromatography-tandem mass spectormetry,LC-MS/MS)技术研究广藿香对贵州小型猪血清代谢的影响,探讨其药理学作用机制。方法将9头贵州小型猪随机分为广藿香给药组(5头)和对照组(4头)。广藿香给药组按0.5 g·头-1·d^(-1)剂量通过拌料经口饲喂广藿香中药配方颗粒,连续给药8 d;对照组正常饲喂,不额外给药。用药结束后采集各组动物的血清样品,采用LC-MS/MS技术分析各组样品的血清代谢物,对代谢组数据进行注释并与KEGG、HMDB和Lipidmaps数据库比对,通过偏最小二乘判别分析(partial least squares discriminant analysis,PLS-DA)、组间聚类、差异代谢物分析和功能富集等生物信息学分析方法,筛选差异代谢生物标志物及其可能的代谢通路。结果在广藿香给药组和对照组的血清样本中共鉴定出443个血清代谢物,筛选出44个差异显著(P<0.05)的代谢物,其中显著上调(P<0.01)的代谢物为肉桂酰甘氨酸、N-苄基-N-异丙基-N'-(4-三氟甲基)苯尿素、亚牛磺酸、D-葡萄糖-6-磷酸、顺-2-癸烯酸、二十碳二烯酸(顺-11,14)、前列腺素A2和10-羟基癸烯酸,显著下调(P<0.01)的代谢物为溶血磷脂酰胆碱22∶5、溶血磷脂酸22∶6和溶血磷脂酸22∶5。差异代谢物主要富集在丙氨酸、天冬氨酸和谷氨酸代谢通路(MapID:map00250),以及牛磺酸和亚牛磺酸代谢通路(MapID:map00430)。结论广藿香能显著影响贵州小型猪的溶血磷脂酸类物质的代谢,可能通过影响天冬氨酸-谷氨酸代谢通路、牛磺酸-亚牛磺酸代谢通路,起到缓解机体氨基酸代谢紊乱、调节炎性反应发生等功能。Objective Based on the liquid chromatography-tandem mass spectormetry(LC-MS/MS),to study the effects of Pogostemon cablin on serum metabolism of Guizhou miniature pigs,and to explore its pharmacological mechanism.Methods Nine healthy Guizhou miniature pigs were divided into two groups,namely Pogostemon cablin drug group(n=5)and control group(n=4).The pigs in Pogostemon cablin drug group were orally fed with traditional Chinese medicine formula granules,each 0.5 g per day,for consecutive 8 days,while those in control group were given normal feeding without additional treatment.After the feeding experiment,serum samples were collected and analyzed using the LC-MS/MS technology.The metabolomics data was annotated and compared with KEGG,HMDB and Lipidmaps databases.Bioinformatics analysis methods including partial least squares discriminant analysis(PLS-DA),intergroup clustering,differential metabolite analysis and functional enrichment were used to screen differential metabolic biomarkers and their possible metabolic pathways.Results Forty-four differential metabolites(P<0.05)were screened out from the 443 metabolites,eight differential metabolites were significantly up-regulated(P<0.01),namely cinnamoylglycine,N-benzyl-N-isopropyl-N'-[4-(trifluoromethoxy)phenyl]urea,hypotaurine,D-glucose 6-phosphate,cis-2-decenoic acid,11(Z),14(Z)-eicosadienoic acid,prostaglandin A2 and 10-hydroxydecanoic acid,and three differential metabolites were significantly downregulated(P<0.01),namely lysophosphatidyl choline 22:5,lysophosphatidic acid 22:6 and lysophosphatidic acid 22:5.The differential metabolites were mainly enriched in the metabolic pathways of alanine,aspartate and glutamate metabolism(MapID:map00250)and taurine and hypotaurine metabolism(MapID:map00430).Conclusion Pogostemon cablin can significantly affect the metabolism of lysophosphatidic acids in porcine,and relieve the disorder of amino acids metabolism and regulate the occurrence of inflammation by affecting the metabolic pathways of alanine,aspartate and glutamat
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