益糖康改善糖尿病肾脏疾病的代谢组学与网络药理学研究  

Metabolomics and network pharmacology study of Yitangkang in improving diabetic kidney disease

作　　者：安琪 石岩[1] 曲超 于嘉祥 张文顺 AN Qi;SHI Yan;QU Chao;YU Jiaxiang;ZHANG Wenshun(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;Second Affiliated Hospital of Liaoning University Traditional Chinese Medicine,Shenyang 110034,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属第二医院,辽宁沈阳110034

出　　处：《沈阳药科大学学报》2024年第6期699-711,共13页Journal of Shenyang Pharmaceutical University

基　　金：辽宁省“兴辽英才计划”项目资助(XLYC2007121)。

摘　　要：目的 联合网络药理学与代谢组学分析益糖康(Yikangtang, YTK)改善糖尿病肾脏疾病(diabetic kidney disease, DKD)的作用机制。方法 64只wistar雄性大鼠,分为空白组(Blank)、模型组(Model)、YTK组、氯沙坦组(LST)各16只。在进行DKD大鼠模型复制并判定成模后给YTK颗粒连续灌胃8w,检测大鼠空腹血糖(fasting blood glucose, FBG)、甘油三酯(triglyceride, TG)、总胆固醇(total cholesterol, TC)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol, LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C),HE染色观察肾脏病理改变。采用超高效液相色谱-四极杆-飞行时间质谱(UPLC-Q-TOF-MS/MS)分析各组大鼠代谢轮廓变化,借助Metabo Analyst数据库查询相关代谢通路。运用网络药理学获取YTK治疗DKD的关键靶点、KEGG富集分析,并构建“代谢物-反应-酶-基因”网络。结果 YTK可显著改善DKD大鼠糖脂代谢水平以及肾脏组织形态。代谢组学初步筛选出16个与YTK治疗DKD密切相关代谢物,主要涉及维生素B6代谢、花生四烯酸代谢等代谢通路。网络药理学结果显示YTK治疗DKD的核心成分为槲皮素、山奈酚、木犀草素等,主要涉及AKT1、TP53、JUN、STAT3等靶蛋白,与癌症信号通路、脂质与动脉粥样硬化通路密切相关,代谢组学与网络药理学联合结果显示,二者均涉及花生四烯酸代谢通路。结论 YTK对DKD具有良好治疗作用,代谢组学和网络药理学分析发现其作用机制可能YTK中槲皮素、山奈酚、木犀草素等通过调控多种代谢物,增强对花生四烯酸代谢通路的影响,为进一步防治DKD提供了依据。Objective In order to explore the mechanism of Yitangkang in ameliorating(diabetic kidney disease,DKD),we use the technology of metabolomics and network pharmacology.Methods Sixty-four male wistar rats were divided into blank group,model group,YTK group and losartan group(LST)with 16 rats in each group.After the DKD rat model was reproduced and established,YTK and LST granules were continuously garaged for 8 weeks.Fasting blood glucose(FBG),triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected,and renal pathological changes were observed by HE staining.Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS)was used to analyze the changes of metabolic profile of rats in each group,and the related metabolic pathways were queried with the help of metabo analyst database.The key target of YTK in treating DKD and KEGG enrichment analysis were obtained by using network pharmacology,and a"metabolite-reaction-enzyme-gene"network was constructed.Results YTK can significantly improve the level of FBG,TC,TG,HDL-C,LDL-C and renal tissue morphology in DKD rats.Metabolomics initially screened out 16 metabolites closely related to YTK in the treatment of DKD,mainly involving vitamin B6 metabolism,arachidonic acid metabolism and other metabolic pathways.The results of network pharmacology demonstrate that the core components of YTK in the treatment DKD are quercetin,kaempferol,luteolin,etc.,which mainly involve AKT1,TP53,JUN,STAT3 and other target proteins,closely related to cancer signaling pathway,lipid and atherosclerosis pathway.The combined results of metabolomics and network pharmacology demonstrate that both of them involve arachidonic acid metabolic pathway.Conclusion YTK has a significant efficacy in the treatment of DKD.Metabolomics and network pharmacology analysis demonstrate its mechanism may be that quercetin,kaempferol and luteolin in YTK enhance the influence on arachidonic acid me

关 键 词：糖尿病肾脏疾病 网络药理学 益糖康 代谢组学 

分 类 号：R28[医药卫生—中药学]