目的 基于网络药理学及 NLRP3 炎症通路探讨丹参保心茶对冠心病合并抑郁症小鼠的作用机制。方法 （1） 利用 TCMSP、BATMAN-TICAM 数据库筛选丹参保心茶的活性成分及其作用靶点；通过 GeneCards、OMIM 数据库筛选冠心病合并抑郁症疾病相关靶点。将丹参保心茶活性成分作用靶点与冠心病合并抑郁症疾病相关靶点导入 Venny 2.1 在线平台，获得二者的交集靶点 （共同靶点） ，即为丹参保心茶治疗冠心病合并抑郁症的潜在作用靶点。通过 STRING 平台对潜在作用靶点进行蛋白互作 （PPI） 网络分析，筛选出关键靶点；构建“药物-活性成分-疾病-靶点”网络，筛选丹参保心茶治疗冠心病合并抑郁症的关键活性成分以及重要靶点；将潜在作用靶点通过 Metascape 数据库进行 GO 功能和 KEGG 通路富集分析。 （2） 将昆明小鼠随机分为 6 组：正常组、模型组、阳性对照组 （酒石酸美托洛尔片 5.14 mg•kg-1+盐酸舍曲林片 10.3 mg•kg-1） 及丹参保心茶高、中、低剂量组 （30.8、15.4、7.7 g•kg-1•d-1） ，每组 8 只。采用慢性不可预知性刺激 （CUMS） 和皮下注射盐酸异丙肾上腺素 （ISO） 诱导冠心病合并抑郁小鼠模型。每天灌胃给药 1 次，连续 18 d。采用行为学实验 （旷场实验、强迫游泳实验、悬尾实验） 检测小鼠抑郁水平；HE、尼氏染色法观察海马组织病理变化；qPCR 法检测海马组织中 IL-6、TNF-α、NLRP3、IL-1β、Caspase-1、IL-10 mRNA 表达水平。结果 （1） 筛选出 65 种丹参活性成分、9 种绿茶活性成分，共得到 1 042 个作用靶点以及 2 116 个冠心病合并抑郁症的疾病相关靶点。将活性成分作用靶点与疾病相关靶点经 Venny 2.1 平台取交集，共得到丹参保心茶治疗冠心病合并抑郁症的潜在作用靶点（共同靶点）299 个。通过潜在作用靶点 PPI 网络分析筛选出 IL-1β、AKT1、TNF-α、IL-6、VEGFA、CASP3、IL-10 等关键靶点。通过“药物-活性成分-疾病-靶点”网络分析得到维生素 B、木犀草素、丹酚酸、丹参酮ⅡA、儿茶素等关键活性成分，以及 PTGS2、IL-1β、IL-6、TNF-α 和 IL-10 等重要靶点。潜在作用靶点主要集中在炎症反应、肿瘤坏死因子调控、糖皮质激素调控、核因子 κB （NF-κB） 转录因子调控等生物过程，以及 PI3K-Akt 信号通路、TNF 信号通路、细胞凋亡信号通路和 NF-κB 信号通路等主要通路。 （2） 与正常组比较，模型组小鼠的旷场总距离和中心距离均显著缩短 （P＜0.01） ，漂浮时间及摇摆不动时间显著延长 （P＜0.01）；海马组织的 IL-6、TNF-α、Caspase-1、NLRP3、IL-1β mRNA 表达均显著上调（P＜0.01），IL-10 mRNA 表达明显下调 （P＜0.05） 。与模型组比较，丹参保心茶高、中、低剂量组小鼠的旷场总距离、中心距离均显著增加 （P＜0.05，P＜0.01） ，漂浮时间及摇摆不动时间显著缩短 （P＜0.01） ；丹参保心茶高、中、低剂量 组小鼠海马组织的 IL-6、IL-1β、NLRP3、TNF-α、Caspase-1 mRNA 表达均显著下调 （P＜0.01） ，丹参保心茶高、中剂量组小鼠海马组织的 IL-10 mRNA 表达显著上调 （P＜0.01） 。结论 丹参保心茶对冠心病合并抑郁症小鼠的干预作用可能是通过木犀草素、丹参酮、丹酚酸、儿茶素等活性成分，作用于 IL-6、TNF-α、IL-1β 和IL-10 等关键靶点，调控 NLRP3 炎症通路来实现的。

Objective To explore the mechanism of action of Danshen Baoxin Cha（DBC） on depressed mice with coronary heart disease （CHD） based on network pharmacology and NLRP3 inflammatory pathway. Methods（1） TCMSP and BATMAN-TICAM databases were used to screen the DBC active ingredients and targets. The targets of CHD with depression were screened using the OMIM and Genecards databases. The targets of DBC active ingredients and related targets of CHD with depression were imported into Venny 2.1 online platform to obtain the intersection targets，which was the potential target of DBC in the treatment of CHD with depression. Protein-protein interaction （PPI） analysis was performed on the intersection targets using the STRING platform to screen the key targets. A "drug- active ingredients - disease- targets" network was created to select the main active ingredients and core targets of DBC for the treatment of CHD with depression. Thereafter，the primary targets were examined by GO function and KEGG pathway enrichment using the Metascape database.（2）Kunming mice were split into six groups of eight mice each at random：the control group，the model group，the positive control group （metoprolol tartrate 5.14 mg•kg-1 + sertraline hydrochloride 10.3 mg•kg-1），and the DBC high-，middle-，and low- dose groups（30.8，15.4 and 7.7 g•kg-1•d-1）. Chronic unpredictable mild stimulation （CUMS） and subcutaneous injection of isoprenaline hydrochloride （ISO） were used to induce a mice model of CHD with depression. Mice were treated orally with the corresponding drug once a day for 18 consecutive days. Behavioral experiments involving forced swimming test， tail suspension test， and open-field test were applied to detect depression levels of mice. Histopathological alterations in hippocampus tissues were noted using HE and Nissl staining. qPCR was used to determine the mRNA expression levels of IL-6，TNF-α，NLRP3，IL-1β，IL-10，and Caspase-1 in hippocampus tissues. Results（1） Sixty-five active components in Salvia and seven active components in green tea were screened out. A total of 1 042 potential targets and 2 116 CHD complicated with depression-related targets were obtained. The intersection of the targets of active components and disease- related targets was performed by Venny 2.1.0 platform to obtain 299 potential targets （common targets） of DBC in the treatment of CHD with depression. The core targets including IL-1β，AKT1，TNF-α，IL-6，VEGFA，CASP3 and IL-10 were screened through PPI network analysis of potential targets. Key active ingredients including vitamin B，luteolin，salvianolic acid，tanshinone IIA and catechin，as well as key targets，such as PTGS2、IL-1β、IL-6、TNF-α and IL-10，were obtained by network analysis of “drugs-active ingredients-disease-targets”. The potential targets were correlated with biological processes such as inflammation response，regulation of tumour necrosis factor （TNF），glucocorticoid regulation，regulation of nuclear factor kappa B（NF-κB） transcription factor，as well as major pathways including PI3K-Akt signaling pathway，TNF signaling pathway，apoptosis signaling pathway，and NF-κB signaling pathway.（2） Compared with the control group，mice in the model group showed a significant decrease in the total and center distance of the open field （P＜0.01） and a significant increase in the time of forced swimming and immobility time of tail suspension test （P＜0.01）. The mRNA expression of IL-6， TNF- α， NLRP3， IL-1β， and Caspase-1 was significantly up-regulated（P＜0.01） in the hippocampus tissues，but IL-10 mRNA expression was down-regulated（P＜0.05）. Compared with the model group，the total and center distance in DBC high-，middle-，and low- dose groups were significantly up-regulated（P＜0.05，P＜0.01），and the time of forced swimming and immobility time of tail suspension test were significantly down-regulated （P＜0.01）. The mRNA expression of IL-6，TNF- α，NLRP3，IL-1β and Caspase-1 of the DBC high-，middle-，and low- dose groups were significantly down-regulated（P＜0.01），IL-10 mRNA expression in mice hippocampus tissue of DBC high- and middle- dose groups was up-regulated （P＜0.01）. Conclusion The intervention effect of DBC on depressed mice with CHD may be achieved by active ingredients including luteolin， tanshinone， salvianolic acid and catechin acting on the key targets，such as IL-6,TNF-α，IL-1β and IL-10，to regulate the NLRP3 inflammatory signaling pathway.

R285.5；R857.3

国家中医药管理局重点研究室研究项目 （20215005）；广东省科技厅重点实验室建设项目 （2022B1212010012）；广东省重点领域研发计划项目 （2020B1111100011）；广东省普通高校重点领域专项 （2022ZDZX2078）；广东省中医药管理局科研项目 （20231246）。