基于血清药物化学的芪蛭益肾胶囊抗糖尿病肾病药效物质基础研究  

Pharmacodynamic material basis of Qizhi Yishen Capsules against diabetic kidney disease based on serum pharmacochemistry

作　　者：刘欣 商桂春 张永清[1] 张传香 崔志明 王迪 刘玉红[1] LIU Xin;SHANG Gui-chun;ZHANG Yong-qing;ZHANG Chuan-xiang;CUI Zhi-ming;WANG Di;LIU Yu-hong(School of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Shandong Phoenix Pharmaceutical Co.,Ltd.,Dongying 257400,China)

机构地区：[1]山东中医药大学药学院,济南250335 [2]山东凤凰制药股份有限公司,东营257400

出　　处：《天然产物研究与开发》2025年第4期624-635,686,共13页Natural Product Research and Development

基　　金：山东省重点研发计划(2022CXGC010511)。

摘　　要：本研究以入血成分为研究对象,结合网络药理学和实验验证,探究芪蛭益肾胶囊(Qizhi Yishen Capsules,QYC)抗糖尿病肾病(diabetic kidney disease,DKD)的药效物质基础。应用UPLC-Q-Exactive-Orbitrap MS/MS技术分析芪蛭益肾胶囊的入血成分,以入血成分为研究对象采用网络药理学方法筛选出QYC抗DKD的关键药效化合物及核心靶点,并利用分子对接技术分析关键药效化合物及核心靶点的结合能力。为进一步确认筛选得到的药效化合物的活性,本研究通过构建两种模型进行实验:一是体外模型,即通过高糖刺激诱导人肾皮质近曲小管上皮细胞(HK-2)损伤,模拟DKD的细胞病理状态;二是体内模型,通过高糖高脂饮食联合链脲佐菌素诱导建立DKD大鼠模型。通过这两种模型对筛选得到的关键药效化合物进行验证。最终共鉴定QYC中23种入血成分;运用网络药理学对入血成分进行分析,结果共筛选得到大黄酸、黄芪甲苷、大黄素、梓醇等9个关键药效成分,EGFR、HSP90AA1等5个核心靶点,成分与靶点分子对接结果良好;细胞及动物实验表明各药效成分可明显改善高糖诱导的HK-2细胞损伤,改善DKD大鼠的肾损伤水平。本研究揭示了QYC抗DKD的关键药效物质,为其进一步的质量标准的制定和临床应用的推广奠定了基础。This study investigates the pharmacodynamic material basis of Qizhi Yishen Capsules(QYC)against diabetic kidney disease(DKD)by focusing on the constituents absorbed into blood,integrating network pharmacology and experimental validation.The constituents absorbed into blood of QYC were identified using UPLC-Q-Exactive-Orbitrap MS/MS technology.Key pharmacodynamic compounds and core targets associated with the anti-DKD effects of QYC were screened through network pharmacology.Additionally,molecular docking techniques were employed to analyze the binding affinity between these key pharmacodynamic compounds and their core targets.This study established two models to further validate the activity of the selected pharmacodynamic compounds.The first model was constructed by inducing injury in human renal cortex proximal tubular epithelial cells(HK-2)via high-glucose stimulation,thereby simulating the cytopathological state characteristic of DKD.The second model was established using a combination of a high-fat and high-sugar diet along with streptozotocin to induce a DKD rat model.The key pharmacodynamic compounds were verified by these two models.In conclusion,a total of 23 constituents absorbed into blood were identified in QYC.Network pharmacology was employed to analyze these components.The results revealed that nine key pharmacodynamic components,including rhein,astragalosideⅣ,emodin,and catalpol were screened,and five core targets,such as EGFR and HSP90AA1 were identified.The results of the molecular docking between the components and the targets were satisfactory.Subsequent cell and animal experiments demonstrated that these pharmacodynamic components could significantly ameliorate HK-2 cell damage induced by high glucose and improve renal injury in DKD rats.This study elucidated the key pharmacodynamic substances of QYC anti-diabetic nephropathy,laying a foundation for further developing quality standards and clinical application promotion.

关 键 词：芪蛭益肾胶囊 糖尿病肾病 UPLC-Q-Exactive-Orbitrap MS/MS 网络药理学 药效物质基础 

分 类 号：R284.1[医药卫生—中药学]