目的 基于网络药理学与分子对接技术，预测名中医验方温阳益气活血方治疗慢性心衰的物质基础及作用机制，通过实验探讨温阳益气活血方对慢性心衰患者外周血基因表达谱的影响，为中医药治疗慢性心衰的后续研究提供基础与方向。方法 通过中药系统药理学分析平台（TCMSP）筛选温阳益气活血方中潜在活性成分；GEO数据库获得潜在活性成分的作用靶点；Venny在线平台获得慢性心衰的主要致病靶标。利用STRING数据库和Cytoscape软件构建"方药-成分-靶点-疾病"网络模型及蛋白相互作用（protein-protein interaction，PPI）网络图，分析方药中主要活性成分及作用靶点蛋白；使用R语言的Cluster Profiler工具包对方药作用核心靶点进行基因本体论（genetic ontology，GO）及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）分析。借助Autodock进行分子对接。随机选取30例健康志愿者作为对照组。60例慢性心衰患者入选试验组，按随机分为化学药组和中西药组，各组30例。化学药组采用盐酸贝那普利片（10 mg/d）、氢氯噻嗪片（50 mg/d）、螺内酯片（40 mg/d）、琥珀酸美托洛尔片（23.75 mg/d）及地高辛片（0.125 mg/d）联合用药，1次/d；中西药组在常规化学药物口服治疗的基础上联合温阳益气活血方颗粒剂，6 g/次，2次/d，2组疗程均为15 d。对照组于清晨空腹安静状态下，抗凝管采集前臂静脉血，后随机抽取10例外周血用于基因芯片的差异检测；试验组于入院次日清晨空腹状态下采集，最后随机抽取2组中各5例药物干预前后的外周血用于基因芯片的差异检测。采用Affymetrix公司的PrimeViewTM Human Gene Expression Array基因芯片检测，结合生物信息学的转录组学及RNA技术分析温阳益气活血方的差异表达基因。结果 筛选出方药潜在活性成分6个和236个药物靶点；得到方药治疗慢性心衰的潜在作用靶点17个；通过GO分析得出519个生物过程、5个细胞组分、14个分子功能；KEGG通路富集分析得出89条信号通路。2组慢性心衰患者给予不同药物干预后，中西药组外周血基因表达谱中共检测出42 640个基因，化学药组为37 081个基因，2种干预方法均能影响慢性心衰外周血的基因表达，单纯化学药较中西药联合干预改变慢性心衰的差异基因数目少。相关检测指标血清脑钠肽前体（brain natriuretic peptide，BNP）、中医症状积分及心功能疗效也具有统计学差异（P<0.05）。结论 初步揭示了温阳益气活血方干预慢性心衰可能是通过多成分、多靶点、多途径发挥防治作用，其作用机制与ZNF331、TRAPPC10、SMAD7、MYC、RORA、PCNA基因相关，涉及Th17细胞分化、B细胞受体信号通路、腺苷酸活化蛋白激酶（adenosine monophosphate activated protein kinase，AMPK）通路。

Objective Based on network pharmacology and molecular docking technology, the material basis and mechanism of Wenyang Yiqi Huoxue Recipe (温阳益气活血方) in the treatment of chronic heart failure were predicted. To explore the effect of Wenyang Yiqi Huoxue Recipe on gene expression profile of peripheral blood in patients with chronic heart failure, so as to provide basis and direction for the follow-up study of traditional Chinese medicine in the treatment of chronic heart failure. Methods Based on the pharmacological analysis platform (TCMSP) of traditional Chinese medicine system, the potential active components of Wenyang Yiqi Huoxue Recipe were screened; GEO database was used to obtain the target of potential active components; Venny online platform was used to obtain the main pathogenic target of chronic heart failure. The "formula-component-target-disease" network model and protein-protein interaction (PPI) network diagram were constructed by using STRING database and Cytoscape software to analyze the main active components and target proteins in prescription; Genetic ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were analyzed by Cluster Profiler toolkit of R language. Autodock was used for molecular docking. Thirty healthy subjects were randomly selected as the control group. Experimental group:Sixty patients with chronic heart failure were randomly divided into chemical medicine group and traditional Chinese medicine (TCM) and Western medicine group. The chemical medicine group was treated with Benazepril Hydrochloride Tablets 10 mg/d, Hydrochlorothiazide Tablets 50 mg/d, Spironolactone Tablets 40 mg/d, Metoprolol Succinate Tablets 23.75 mg/d and Digoxin Tablets 0.125 mg/d, 1 time/d; On the basis of oral treatment with conventional chemical drugs, the TCM and Western medicine group was combined with Wenyang Yiqi Huoxue Formula Granules, 6 g/time, 2 times/d. The course of treatment of both groups was 15 d. In the control group, venous blood of forearm was collected by anticoagulant tube in the quiet state of fasting in the morning, and then 10 cases of peripheral blood were randomly selected for differential detection of gene chip. The experimental group was collected on an empty stomach in the morning of the next day after admission, the peripheral blood of five cases in each group was randomly selected for the difference detection of gene chip before and after drug intervention. Affymetrix company's PrimeViewTM Human Gene Expression Array Gene chip was used to detect the reverse differentially expressed genes of Wenyang Yiqi Huoxue Recipe combined with bioinformatics transcriptome and RNA technology. Results Six potential active components and 236 drug targets were screened; Seventeen potential targets of prescriptions in the treatment of chronic heart failure were obtained; A total of 519 biological processes, five cell components and 14 molecular functions were obtained by GO analysis; Eighty-nine signal pathways were obtained by KEGG pathway enrichment analysis. Microarray experiment showed that after the two groups of patients with chronic heart failure were given different drugs, a total of 42 640 genes were detected in the gene expression profile of peripheral blood in the TCM and Western medicine group and 37 081 in the chemical medicine group. Both intervention methods can affect the gene expression of peripheral blood of chronic heart failure. The number of differential genes of chronic heart failure changed by single pure chemical drugs was less than that by the combined intervention of Chinese and Western medicine.There were also significant differences in related indexes brain natriuretic peptide (BNP), TCM symptom score and cardiac function (P<0.05). Conclusion It is preliminarily revealed that Wenyang Yiqi Huoxue Recipe may play a preventive and therapeutic role in chronic heart failure through multiple components, multiple targets and multiple ways. Its mechanism is related to ZNF331, TRAPPC10, SMAD7, MYC, RORA and PCNA genes, involving Th17 cell differentiation, B cell receptor signal pathway and adenosine monophosphate activated protein kinase (AMPK) pathway.

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教育部春晖计划项目（Z2017056）；青海省高层次卫生人才（领军人才）项目（2018年，2019年）；青海省中藏医药科研创新项目（J2020005，J2020007）；青海省卫生健康委员会重点项目（2019-wjzd-11）；青海省应用基础研究项目（2016-ZJ-777）；2018年中医药公共卫生服务补助专项“全国中药资源普查项目”（财社[2018]43号）；青海省糖脂代谢疾病防控中医药重点实验室开放课题