结合网络药理学和实验验证，探讨补肾强心方治疗慢性心力衰竭的作用机制

Pharmacological Research - Modern Chinese Medicine Pub Date : 2025-01-23 DOI:10.1016/j.prmcm.2025.100579

Jinhua Pang , Jiejun Hou , Jinyi Chen , Wenchu Zhao , Tiantian Tang , Taotao Li , Ding Liu , Jinkai Li , Xuan Wang

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引用次数: 0

摘要

目的：以网络药理学和实验动物学为基础，探讨补肾强心方治疗慢性心力衰竭的作用机制。方法：基于网络药理学和基因表达综合数据库（Gene Expression Omnibus， GEO）的数据，对BSQX在CHF中的靶点和成分进行评估。构建药物-疾病相互作用网络图，分析BSQX在CHF中可能影响的途径。利用Discovery Studio软件对BSQX关键组分与CHF关键靶点进行分子对接。最后，建立CHF大鼠模型。采用酶联免疫吸附法测定各组大鼠血清白细胞介素(IL)-6水平。苏木精法观察左室心肌组织结构变化；通过免疫组化检测心肌组织cTnI、IL-17、NF-KB蛋白的表达。结果：利用网络药理学和GSE84796数据库的数据筛选BSQX治疗CHF的25个核心靶点。通过Gene Ontology和Kyoto Encyclopedia of Genes and Genomes富集分析，确定了与糖尿病并发症、脂质和动脉粥样硬化相关的主要信号通路，包括IL-17信号通路、肿瘤坏死因子信号通路、AGE-RAGE信号通路。分子对接结果显示，核心靶点（IL6、MMP9、CCL2、STAT1）与活性物质（槲皮素、木质醇、齐墩果酸、五糖酸、异桦木酸）结合良好。苏木精和动物实验伊红染色显示，BSQX能在一定程度上减轻CHF心肌细胞的炎症浸润和纤维化程度。酶联免疫吸附实验和免疫组织化学表明，BSQX能有效降低慢性大鼠IL-17、IL-6、cTnI和NF-KB水平。结论：基于网络药理学和实验动物研究，BSQX在CHF治疗中的作用机制可能与抑制IL-17、IL-6、cTnI和NF-KB的产生，抑制炎症细胞浸润，减轻心肌损伤有关。此外，其作用机制可能通过IL-17信号通路发挥作用。

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Integrating network pharmacology and experimental validation to explore the mechanism of action of BushenQiangxin Formula for the treatment of chronic heart failure

Objective

: To evaluate the mechanism of action of the BushenQiangxin (BSQX) formula in treating chronic heart failure (CHF) based on network pharmacology and experimental zoology.

Methods

: The targets and components of BSQX in CHF were assessed based on network pharmacology and data from the Gene Expression Omnibus (GEO) database. The drug–disease interaction network diagram was constructed, and the possible pathways affected by BSQX in CHF were analyzed. Molecular docking between the key components of BSQX and the key targets of CHF was performed using the Discovery Studio software. Finally, a CHF rat model was established. The serum interleukin (IL)-6 level was evaluated using the enzyme-linked immunosorbent assay in each rat group. The structural changes in the left ventricular myocardial tissues were observed via hematoxylin & eosin staining, and the expression of cTnI, IL-17, and nuclear factor kappa B (NF-KB) proteins was measured via immunohistochemistry in the cardiac muscle tissue.

Results

: Network pharmacology and data from the GSE84796 database were used to screen 25 core targets of BSQX for CHF. The major signaling pathways, including the IL-17 signaling pathway, tumor necrosis factor signaling pathway, AGE-RAGE signaling pathway, which are associated with diabetic complications, lipid, and atherosclerosis were identified via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The molecular docking results showed good binding between the core targets (IL6, MMP9, CCL2, and STAT1) and active compounds (such as quercetin, lignocerol, oleanolic acid, pentacosanoic acid, and isobetulinic acid). Hematoxylin & eosin staining in animal experiments showed that BSQX could reduce the degree of inflammatory infiltration and fibrosis of cardiomyocytes in CHF to a certain extent. The enzyme-linked immunosorbent assay and immunohistochemistry showed that BSQX could effectively reduce the levels of IL-17, IL-6, cTnI, and NF-KB in chronic rats.

Conclusion

: In CHF treatment, the mechanism of BSQX can be related to the inhibition of IL-17, IL-6, cTnI, and NF-KB production, inflammatory cell infiltration, and the attenuation of myocardial injury based on network pharmacology and experimental animal studies. Moreover, its mechanism of action may function via the IL-17 signaling pathway.

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来源期刊

Pharmacological Research - Modern Chinese Medicine

CiteScore

1.60

自引率

0.00%

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