基于代谢组学探讨二陈汤对痰证小鼠结直肠代谢物的影响  

Effect of Erchen Decoction on Colorectal Metabolites in Mice with Phlegm Syndrome Based on Metabolomics

作　　者：李晓君 丁珊珊[1] 刘思祎 隆卫阳 廖凌虹[1] LI Xiaojun;DING Shanshan;LIU Siyi;LONG Weiyang;LIAO Linghong(Traditional Chinese Medicine Syndrome Research Base,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学中医证研究基地,福建福州350122

出　　处：《中医药学报》2023年第11期55-62,共8页Acta Chinese Medicine and Pharmacology

基　　金：福建省科技厅自然科学基金-高校联合-面上项目(2018J01893);福建省科技厅自然科学基金项目(2020J01740)。

摘　　要：目的:基于超高效液相色谱-质谱联用(UHPLC-QE-MS)技术的代谢组学方法,寻找与痰证相关的潜在生物标志物,探讨二陈汤对痰证小鼠结直肠代谢物的影响。方法:采用高脂饮食方法建立痰证小鼠模型,将C57BL/6J小鼠随机分为正常组、痰证模型组、二陈汤组。检测小鼠体质量与血脂指标;运用UHPLC-QE-MS技术分析各组小鼠结直肠组织代谢物,正交偏最小二乘法-判别分析(OPLS-DA),结合t检验和变量投影重要性(VIP)筛选与证候相关的生物标志物,使用KEGG数据库对筛选出的差异代谢物进行可能的代谢通路分析。结果:与正常组相比,痰证模型组小鼠体质量、甘油三酯、胆固醇以及高密度脂蛋白显著升高(P<0.01),二陈汤干预后痰证组小鼠体质量、甘油三酯、胆固醇以及高密度脂蛋白呈现下降趋势,其中体质量以及甘油三酯明显降低(P<0.01)。采用UHPLC-QE-MS筛选出正常组与痰证模型组、痰证模型组与二陈汤组共有且存在相反趋势的差异代谢物12个,二陈汤上调了5个差异代谢物,下调了7个差异代谢物,其中显著上调了异戊酰甘氨酸(Isovalerylglycine)和焦磷酸盐(Pyrophosphate)2个差异代谢物(P<0.05),差异代谢物主要富集在烟酸和烟酰胺代谢等5条代谢通路。结论:二陈汤具有调控烟酸和烟酰胺代谢等代谢途径的作用,是其化痰的潜在机制,异戊酰甘氨酸和焦磷酸盐作为痰证的潜在生物标志物,有待进一步研究。Objective:To search for potential biomarkers related to phlegm syndrome based on metabolomics method of ultra high performance liquid chromatography mass spectrometry(UHPLC-QE-MS)and explore the effect of Erchen decoction on colorectal metabolites in mice with phlegm syndrome.Methods:The model of phlegm syndrome was established by high fat diet.C57BL/6J mice were randomly divided into normal group,phlegm syndrome model group and Erchen decoction group.The indexes of body mass and blood lipid of mice were detected.UHPLC-QE-MS technology was used to analyze the colorectal tissue metabolites of mice in each group,data were processed through orthogonal partial least squares discriminant analysis(OPLS-DA),T-test and variable projection importance(VIP)were combined to screen biomarkers associated with the syndrome,and KEGG database was employed to analyze the possible metabolic pathways of the selected differential metabolites.Results:Compared with the normal group,the body weight,triglyceride,cholesterol and high-density lipoprotein of the phlegm syndrome model group mice increased significantly(P<0.001).After the intervention by Erchen decoction,the body weight,triglyceride,cholesterol and high-density lipoprotein of the phlegm syndrome group mice showed a downward trend,and the body weight(P<0.05)and triglyceride(P<0.01)decreased significantly.12 differential metabolites shared with opposite trend between normal group mice and phlegm syndrome model group mice,and between phlegm syndrome model group mice and Erchen decoction group mice were screened out through UHPLC-QE-MS.Erchen decoction up-regulated 5 differential metabolites and down-regulated 7 differential metabolites,and 2 of the differential metabolites,isovalerylglycine and pyrophosphate,were significantly increased(P<0.05).The differential metabolites were mainly concentrated in five metabolic pathways,including nicotinic acid and nicotinamide metabolism.Conclusion:Erchen decoction can regulate the metabolism of nicotinic acid and nicotinamide,which is the

关 键 词：痰证 二陈汤 异戊酰甘氨酸 焦磷酸盐 烟酸和烟酰胺代谢 

分 类 号：R285.5[医药卫生—中药学]