文献类型：期刊文献

中文题名：基于网络药理学及实验验证的芪参益心颗粒干预慢性心力衰竭机制研究

英文题名：Study on Intervention Mechanism of Qishen Yixin Granules on Chronic Heart Failure Based on Network Pharmacology and Experimental Validation

作者：马睿玲[1,2];贾冠军[1,3];吕红英[1];王怡园[1,2];张玲娜[1,2];康万荣[4];徐晓东[3];卢玉俊[3];李应东[1,2,3];伊琳[1,2]

第一作者：马睿玲

机构：[1]甘肃中医药大学中西医结合学院,甘肃兰州730030;[2]甘肃省中医药防治慢性疾病重点实验室,甘肃兰州730030;[3]甘肃中医药大学附属医院,甘肃兰州730030;[4]甘肃中医药大学科研实验中心,甘肃兰州730030

第一机构：甘肃中医药大学中西医结合学院

年份：2026

卷号：33

期号：3

起止页码：26

中文期刊名：中国中医药信息杂志

外文期刊名：Chinese Journal of Information on Traditional Chinese Medicine

基金：国家自然科学基金(82160842);甘肃省联合科研基金一般项目(23JRRA1521);甘肃省教育厅高校教师创新基金项目(2026A-112);甘肃省自然科学基金(24JRRA1019)。

语种：中文

中文关键词：网络药理学;芪参益心颗粒;慢性心力衰竭;基质金属蛋白酶2;肿瘤坏死因子-α;p38丝裂原活化蛋白激酶;环磷腺苷效应元件结合蛋白1

外文关键词：network pharmacology;Qishen Yixin Granules;chronic heart failure;MMP2;TNF-α;p38 MAPK;CREB1

摘要：目的基于网络药理学和实验验证探讨芪参益心颗粒干预慢性心力衰竭(CHF)的作用机制。方法通过TCMSP数据库筛选芪参益心颗粒活性成分及其靶点,通过OMIM、GeneCards、TTD、DrugBank数据库获取CHF靶点,将药物靶点与疾病靶点取交集,构建蛋白相互作用网络并筛选核心靶点,进行GO和KEGG通路富集分析。将药物关键成分与核心靶点进行分子对接。采用盐酸阿霉素腹腔注射诱导CHF大鼠模型,将大鼠随机分为对照组、模型组、芪苈强心胶囊组及芪参益心颗粒低、中、高剂量组,并予相应干预,连续3周,检测心功能指标左室射血分数(LVEF)、左室短轴缩短率(LVFS)及血清氨基末端脑钠肽前体(NT-proBNP)含量,HE染色、Masson染色观察心肌组织形态,免疫组化染色检测心肌组织基质金属蛋白酶2(MMP2)表达,RT-qPCR、Western blot检测心肌组织TNF-α/p38 MAPK/CREB1通路mRNA及蛋白表达。结果网络药理学筛选出木犀草素、槲皮素等芪参益心颗粒关键成分,富集分析显示MAPK、HIF-1、NF-κB信号通路为关键通路。动物实验显示,芪参益心颗粒可减轻模型大鼠心肌组织病理变化,升高LVEF和LVFS,降低血清NT-proBNP含量(P<0.01),改善心肌纤维化,下调心肌组织MMP2表达及TNF-α、p38 MAPK、CREB1 mRNA和蛋白表达(P<0.05,P<0.01)。结论芪参益心颗粒可能通过调控MMP2表达及TNF-α/p38 MAPK/CREB1信号通路,抑制炎症反应和心肌纤维化,从而改善心功能。
Objective To investigate the mechanism of Qishen Yixin Granules on chronic heart failure(CHF)through network pharmacology and experimental validation.Methods Active components and targets of Qishen Yixin Granules were screened from TCMSP database.CHF-related targets were obtained from OMIM,GeneCards,TTD and DrugBank databases.The drug targets and disease targets were intersected,the protein-protein interaction network was constructed and the core targets were screened,and GO and KEGG pathways were enriched and analyzed.Molecular docking was performed to validate interactions between core components and targets.A CHF rat model was established by intraperitoneal injection of doxorubicin hydrochloride.Rats were randomly divided into control group,model group,Qili Qiangxin Capsule group,and Qishen Yixin Granules low-,medium-,high-dosage group.After 3 weeks of intervention,cardiac function(LVEF,LVFS)and serum NT-proBNP levels were detected.HE staining and Masson staining were used to observe the morphology of myocardial tissue.The expression of MMP2 was detected by immunohistochemistry,and the mRNA and protein expressions of TNF-α/p38 MAPK/CREB1 pathway of myocardial tissue were detected by RT-qPCR and Western blot.Results Network pharmacology identified key components including luteolin and quercetin in Qishen Yixin Granules.Enrichment analysis revealed MAPK,HIF-1 and NF-κB pathways as key pathways.Animal experiment results showed that Qishen Yixin Granules alleviated myocardial pathological changes,improved LVEF and LVFS,reduced serum content of NT-proBNP(P<0.01),attenuated myocardial fibrosis,and down-regulated mRNA and protein expressions of MMP2,TNF-α,p38 MAPK and CREB1(P<0.05,P<0.01).Conclusion Qishen Yixin Granules may inhibit inflammatory reaction and myocardial fibrosis by regulating the expression of MMP2 and TNF-α/p38 MAPK/CREB1 signaling pathway,so as to improve cardiac function.