基于肾脏代谢组学探讨黄芩汤对DN模型小鼠的调节作用

To investigate the regulatory effect of Huangqin Decoctien on DN model mice based on kidney metabolomics

目的基于肾脏代谢组学的方法探讨黄芩汤对DN(糖尿病肾病)防治作用的作用机制,并通过寻找具有生物学意义的内源性潜在生物标志物,以此探寻其相关代谢通路。方法db转基因小鼠购入后适应性饲养1周后,选择血糖值高于11.1mol/L的db/db小鼠进行分组,分为模型组、黄芩汤组(11.25g/kg)、阳性药组(二甲双胍250mg/kg),db/m小鼠为空白组,分组后每天给药一次,给药体积为7.5ml/kg,连续给药8周,并采用UPLC-Q-TOF-MS技术对空白组、模型组、黄芩汤组小鼠肾脏代谢组学进行分析,采用主成分分析法探寻潜在的关键性生物标志物,联合人类代谢组学数据库(HMDB)和京都基因与基因组百科全书数据库(KEGG)找出对应对的相关性代谢通路。结果黄芩汤组可改善DN模型小鼠代谢轨迹的偏离,同时,寻找出与DN模型及给予黄芩汤干预后具有共同差异的生物标志物15个,涉及12条相关代谢通路,应用相关代谢通路分析发现,影响最为广泛的代谢通路可能是甘油磷脂代谢、嘌呤代谢、亚油酸代谢、嘧啶代谢。结论黄芩汤对DN模型小鼠肾脏代谢产物具有调节作用,为进一步对黄芩汤治疗相关疾病的临床安全应用提供理论依据。

Objective To explore the therapeutic mechanism of Huangqin Decoctien on DN(diabetic nephropathy),and explore the biological significance.Methods db/db mice with 11.1 mol/L for group were divided into model group,Huangqin Decoctien administration group(11.25 g/kg),positive drug group(metformin 250 mg/kg),db/m mice were blankgroup,administered once a day after group,administration volume of 7.5 ml/kg and continuous administration for 8 weeks.Using UPLC-Q-TOF-MS technology,the blank group,model group and Huangqin Decoctien group were analyzed to explore potential key biomarkers,and combined with the human metabolomics database(HMDB)and the Kyoto Gene and Genomics Encyclopedia Database(KEGG)to find out the corresponding related metabolic pathway.Results Huangqin Decoctien can improve the deviation of mouse metabolic trajectory,at the same time,find with the DN model and intervention biomarker 15,involving 12 related metabolic pathway,using related metabolic pathway analysis found that the most widely affected metabolic pathway may be glycerol phospholipid metabolism,purine metabolism,linoleic acid metabolism,pyrimidine metabolism.Conclusion Huangqin Decoctien has regulatory effect on kidney metabolism of DN model mice and provides theoretical basis for further clinical safety application of Huangqin Decoctien for related diseases.