基于网络药理学与药理实验验证探讨黄葵胶囊治疗慢性肾炎的作用机制  

Action Mechanism of Huangkui Capsule in Treating Chronic Nephritis Based on Network Pharmacology and Pharmacological Experiment

作　　者：邹佳 王富江 葛海涛 李璠 ZOU Jia;WANG Fujiang;GE Haitao;LI Fan(School of Pharmacy,Kunming Medical University,Yunnan Key Laboratory of Natural Drug Pharmacology,Kunming 650500,China;Jiangsu Suzhong Pharmaceutical Research Institute Co,.LTD.,Nanjing 210031,China)

机构地区：[1]昆明医科大学药学院暨云南省天然药物药理重点实验室,云南昆明650500 [2]江苏苏中药业研究院有限公司,江苏南京210031

出　　处：《中医药信息》2023年第6期44-53,共10页Information on Traditional Chinese Medicine

基　　金：国家中医药管理局中医药科学技术研究专项项目(GZY-KJS-2019-017);校企联合基金-2021年南京中医药大学自然科学基金项目(XZR2020099)。

摘　　要：目的:基于网络药理学和药理实验探索黄葵胶囊治疗慢性肾炎的药效及作用机制。方法:通过文献挖掘并结合PubChem数据库收集黄葵胶囊成分及相关信息,使用SwissTargetPrediction和GeneCards数据库分别预测药物靶点与慢性肾炎疾病靶点,利用STRING数据库和Cytoscape 3.8.0软件进行蛋白互作和拓扑分析并筛选核心靶点,Metescape平台对核心靶点进行京都基因和基因组百科全书(KEGG)富集分析和基因本体(GO)富集分析。32只SD大鼠建立慢性肾小球肾炎大鼠模型,随机分为模型组、氯沙坦钾组以及黄葵胶囊中剂量组(HKJ-M)、黄葵胶囊高剂量组(HKJ-H),每组8只;另取8只SD大鼠为正常组。各组分别给予相应药物灌胃4周,观察各组大鼠肾组织病理学变化,检测24 h尿蛋白含量、血肌酐、血尿素氮、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、血清丙二醛(MDA)和超氧化物歧化酶(SOD)水平。结果:通过网络药理学收集整理得到57个黄葵胶囊治疗慢性肾炎潜在作用靶点,筛选出TNF、MMP9和IL2等炎症相关核心靶点及MAPK、TNF和IL-17等炎症信号通路治疗慢性肾炎。动物实验结果表明,黄葵胶囊能明显改善模型大鼠一般状态;HE染色发现肾小球体积增大有所减轻,PAS染色基底膜增厚程度减轻,“钉突”较少见;经黄芪胶囊干预后,慢性肾炎大鼠24h尿蛋白含量、ACR、血尿素氮、血肌酐、TNF-α、IL-6、MDA水平显著下降(P<0.05),SOD水平明显升高(P<0.05)。结论:黄葵胶囊可能通过调控TNF等炎症信号通路减轻炎症因子的表达从而起到对慢性肾炎的治疗效果。Objective:To explore the efficacy and mechanism of Huangkui Capsule in treating chronic nephritis based on network pharmacology and pharmacological experiment.Methods:The chemical constituents of Huangkui Capsule were collected through literature mining and combined with PubChem databases,drug targets and chronic nephritis disease targets were predicted by databases of SwissTargetPrediction and GeneCards,respectively.After taking the intersection targets,STRING database and Cytoscape 3.8.0 software were used for protein interaction and topological analysis to screen core targets,and Metescape platform was used for Kyoto Encyclopedia of Genes,Genomes(KEGG)and gene ontology(GO)enrichment analysis of these core targets.32 SD rats were established the model of chronic glomerulonephritis,and were randomly divided into the model group,the Losartan Potassium group and the Huangkui Capsule groups of medium-dose and high-dose,with 8 rats in each group.After 4 weeks of corresponding intervention in each group,the histopathological changes of kidneys were observed,and 24 h urine protein content,the levels of serum creatinine,blood urea nitrogen,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),serum malondialdehyde(MDA)and superoxide dismutase(SOD)were measured in each group.Results:Through network pharmacological collection and sorting,57 potential targets of Huangkui Capsule for chronic glomerulonephritis were obtained,and the core targets related to inflammation,including TNF,MMP-9 and IL-2,were screened;inflammatory signaling pathways,such as MAPK,TNF and IL-17,were used to treat chronic nephritis.The results of animal experiments showed that Huangkui Capsule could significantly improve the general state of the rats;HE staining found that the increased volume of glomerulus was decreased,PAS staining showed that the thickened bottom membrane was alleviated,and‘spikes’were rarely seen.The levels of 24 h urine protein,serum creatinine,TNF-α,IL-6 and MDA were significantly decreased(P<0.05),and the level of SOD was

关 键 词：黄葵胶囊 慢性肾炎 网络药理学 炎症 作用机制 信号通路 

分 类 号：R285.5[医药卫生—中药学]