拆方理论结合网络药理学考证利湿名方五苓散保护肾功能的配伍合理性  

Research on the Compatibility Rationality of Wuling Powder(五苓散) in Protecting Renal Function:A Study Based on Prescription Decomposition Theory Combined with Network Pharmacology

作　　者：李泽宇 郝二伟[1,2,3] 曹瑞 林思 李瑞林 沈玉彬 梁玲玲 侯小涛 邓家刚[1,2,3] LI Zeyu;HAO Erwei;CAO Rui;LIN Si;LI Ruilin;SHEN Yubin;LIANG Lingling;HOU Xiaotao;DENG Jiagang(China-ASEAN Joint Laboratory for International Cooperation in Traditional Medicine Research,Guangxi University of Chinese Medicine,Nanning 530200;Guangxi Key Laboratory of Theory and Transformation of Traditional Chinese Medicine Prescriptions for Damp Diseases,Nanning 530200;Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica,Nanning 530200)

机构地区：[1]广西中医药大学中国-东盟传统药物研究国际合作联合实验室,南宁530200 [2]广西中医湿病方药理论与转化重点实验室,南宁530200 [3]广西中药药效研究重点实验室,南宁530000

出　　处：《中药药理与临床》2023年第6期8-16,共9页Pharmacology and Clinics of Chinese Materia Medica

基　　金：中国-东盟传统药物研究国际合作联合实验室建设(二期)项目(编号:AD19110165);广西科技重大专项项目(编号:桂科AA19254033-2)。

摘　　要：目的:应用传统中医药拆方理论和现代网络药理学分析方法考察经典利湿名方五苓散(茯苓、猪苓、泽泻、白术、桂枝)保护肾功能的配伍合理性。方法:应用中医药方剂配伍中的“君-臣-佐”法则将五苓散进行拆方分组,在TCMSP网站获取君药、臣药、佐药的活性化合物,并在TCMSP、SWISS Target Prediction平台获取这些化合物的作用靶点,在Genecards、DisGeNET、OMIM数据库获取保护肾功能靶点,药物与功效靶点取交集后得到五苓散各拆方组保护肾功能的作用靶点,将这些作用靶点按照“君-臣-佐”进行拆分,进行相关蛋白互作、作用通路及生物功能分析,并基于拆方网络药理学分析结果,考查“君-臣-佐”对特征性共表达基因的影响,以佐证其联合增效的作用。结果:五苓散“君-臣-佐”共同调控核心靶点蛋白激酶B(AKT1)、肿瘤坏死因子(TNF)、白介素6(IL6)、丝裂原活化蛋白激酶3(MAPK3)、表皮生长因子受体(EGFR)、雌激素受体1(ESR1)、前列腺素内过氧化物合酶2(PTGS2)等发挥保护肾功能作用,其中臣药白术特征性调控核心靶点为白介素1β(IL1B)、髓过氧化物酶(MPO)、CA9,佐药桂枝特征性调控核心靶点为基质金属蛋白酶9(MMP9)、醛糖还原酶(AKR1B1)、芳香烃受体(AHR),君药保护肾功能主要作用通路为糖尿病并发症中的cAMP信号通路、AGE-RAGE信号通路、cGMP-PKG信号通路、等,“臣-佐”还特征性贡献了糖尿病心肌病、脂肪细胞脂解调节、TRP通道炎症介质调节、等作用通路,“臣-佐”中的差异靶点IL1B、血红素加氧酶-1(HMOX1)、Toll样受体4(TLR4)、F3、MMP9、组蛋白脱乙酰基酶2(HDAC2)可增强对PI3K-AKT信号通路、Rap1信号通路、甲状腺激素信号通路、TNF信号通路、Toll样受体信号通路、MAPK信号通路等的调控,差异靶点毒蕈碱型胆碱受体M3(CHRM3)、MPO、TLR4、等也参与细胞对氮化合物的反应、细胞对有机氮化合物的反�Objective:To investigate the compatibility rationality of Wuling Powder(五苓散) [Fuling(茯苓),Zhuling(猪苓),Zexie(泽泻),Baizhu(白术),and Guizhi(桂枝)] in protecting renal function based on the prescription decomposition theory and network pharmacology.Methods:Firstly,the prescription of Wuling Powder was decomposed according to the rule of Jun(君)-Chen(臣)-Zuo(佐) in the compatibility of Chinese medicine prescriptions,and then the active compounds of Jun,Chen,and Zuo medicines were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The targets of these compounds were predicted by TCMSP and SWISS Target Prediction,and the targets for protecting renal function by Genecards,DisGeNET,and OMIM.The common targets shared by the active compounds and renal protection were identified as the targets involved in the protection of renal function by Wuling Powder.These targets were separated according to the rule of Jun-Chen-Zuo and then the protein-protein interaction,signaling pathways,and biological functions were analyzed.On the basis of the results of network pharmacological analysis,we studied the effects of Jun,Chen,and Zuo medicines on characteristic co-expressed genes to prove their synergistic effect.Results:The Jun,Chen,and Zuo medicines of Wuling Powder jointly regulated the core targets protein kinase B(AKT1),tumor necrosis factor(TNF),interleukin-6(IL-6),mitogen-activated protein kinase 3(MAPK3),epidermal growth factor receptor(EGFR),estrogen receptor 1(ESR1),and prostaglandin-endoperoxide synthase 2(PTGS2) to protect renal function.Baizhu,the Chen medicine in the prescription,specifically regulated the core targets interleukin-1β(IL-1β),myeloperoxidase(MPO),and carbonic anhydrase(CA9).Guizhi,the Zuo medicine,specifically regulated the core targets matrix metalloproteinase 9(MMP9),aldo-keto reductase family 1,member B1(AKR1B1),and aromatic hydrocarbon receptor(AHR).The Jun medicine mainly protected renal function via the cyclic adenosine mon

关 键 词：五苓散 拆方 网络药理学 肾功能 配伍 实验验证 

分 类 号：R285[医药卫生—中药学]