目的 基于超高效液相色谱-四极杆飞行时间质谱（ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry，UHPLC-QTOF-MS/MS）技术和中医药整合药理学研究平台（Chinese Medicine Integrated Pharmacology Research Platform，TCMIP）v2.0筛选牡丹皮治疗慢性肾炎的活性成分，并初步分析其作用机制。方法 采用UHPLC-QTOF-MS/MS，分别在正、负离子扫描模式下对牡丹皮化学成分进行定性分析；基于TCMIP v2.0收集牡丹皮的候选靶标谱和慢性肾炎的基因集；基于TCMIP v2.0平台构建上述靶标间的蛋白间相互作用（protein-protein interaction，PPI）网络，根据网络特征值确定核心靶标；通过DAVID v6.8软件（http://david.abcc.ncifcrf.gov/）进行基因本体论（genetic ontology，GO）功能分析和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析，筛选与慢性肾炎相关的通路作为核心通路；圈定核心通路对应靶标的化学成分，统计每个成分的靶点数量、靶点频次、成分含量；根据统计结果确定牡丹皮治疗慢性肾炎的核心成分；利用Cytoscape 3.8.0软件构建“成分-靶标-通路”多维关联网络。结果 在正、负离子模式下共鉴定了牡丹皮中73个化学成分；通过分析PPI相互作用网络获得123个核心节点；KEGG富集分析确定了17条慢性肾炎相关通路；通过靶点数量、频次和响应值综合筛选得到13个核心成分。结论 牡丹皮中的13个核心成分可能通过调控核因子-κB（nuclear factor-κB，NF-κB）通路、肾素分泌通路、磷脂酰肌醇-3-羟激酶（phosphatidylinositol-3-hydroxykinase，PI3K）/蛋白激酶B（protein kinase B，Akt）通路等17条通路治疗慢性肾炎，为进一步研究牡丹皮治疗慢性肾炎的作用机制奠定了数据基础。

Objective To screen the active components of Mudanpi (Moutan Cortex) in the treatment of chronic nephritis based on ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS/MS) and Chinese Medicine Integrated Pharmacology Research Platform (TCMIP v2.0). The mechanism of action was analyzed. Methods UHPLC-QTOF-MS/MS was used to qualitatively analyze the chemical components of Moutan Cortex in positive and negative ion scanning mode, respectively; The candidate target spectrum of Moutan Cortex and the gene set of chronic nephritis were collected based on TCMIP v2.0; The protein-protein interaction (PPI) network between the above targets was constructed based on TCMIP v2.0 platform, and the core targets of the network was determined according to the network eigenvalues. Gene ontology (GO) functional analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were carried out by DAVID v6.8 software (http://david.abcc.ncifcrf.gov/), the pathways associated with chronic nephritis was selected as the core pathway; The chemical components of the corresponding targets of the core pathways were delineated, and the number of targets, target frequency and component content of each component were counted; the core components of Moutan Cortex in the treatment of chronic nephritis were determined according to the statistical results. Cytoscape 3.8.0 software was used to construct the "component-target-pathway" multi-dimensional association network. Results A total of 73 chemical constituents in Moutan Cortex were identified in positive and negative ion modes; 123 core nodes were obtained by analyzing the PPI interaction network; 17 pathways associated with chronic nephritis were enriched by KEGG enrichment analysis; 13 key active ingredients were obtained through comprehensive screening of response values. Conclusion The 13 key active components in Moutan Cortex may treat chronic nephritis by regulating 17 pathways such as nuclear factor-κB (NF-κB) signaling pathway, phosphatidylinositol-3-hydroxykinase (PI3K)/protein kinase B (Akt) signaling pathway, etc. The results lay a certain foundation for further research on the mechanism of Moutan Cortex in the treatment of chronic nephritis.

R284;R285

中国中医科学院科技创新工程（C12021A04904）