Wang Anzhu, Zhao Wei, Yan Kaituo, Guo Lijun, Gao Feng, Chen Jingjing, Wang Yifei, Ma Xiaochang
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Graduate School, China Academy of Chinese Medical Sciences, Beijing, China.
Front Pharmacol. 2022 Sep 26;13:1004929. doi: 10.3389/fphar.2022.1004929. eCollection 2022.
Under Chinese medicine theory guidance, Fuzheng Yangxin Recipe (FZYX) is clinically effective for the treatment of heart failure (HF) caused by ischemic heart disease (IHD). This study aimed to investigate the mechanism of the myocardial protective effects of FZYX on HF. The Gene expression omnibus database was used to identify differential genes of the IHD subtype. Through network pharmacological methods, the targets of the active components of FZYX were obtained. We also constructed IHD-induced HF model rats by ligating the left anterior descending coronary artery. Echocardiography, pathological section staining, enzyme-linked immunosorbent assay, western blotting, immunohistochemistry, and quantitative real-time PCR analyses were performed to verify the protective effects of FZYX on the myocardium. We identified 53 active components and 37 potential targets of FZYX associated with the IHD subtype. Signal transducer and activator of transcription 3 (STAT3) is a key protein in the protein-protein interaction (PPI) network. A total of 146 biological processes, 10 cellular components and 40 molecular function subcategories were identified by Gene Ontology (GO) enrichment analysis, and 18 signalling pathways, including apoptosis, were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. experiments showed that FZYX significantly inhibited cardiomyocyte apoptosis, promoted the expression and phosphorylation of STAT3, and improved cardiac function. FZXY improves cardiac function and protects cardiomyocytes from injury via multi-component, multi-target and multi-pathway action, especially its possible role in regulating STAT3 expression and anti-apoptotic effect.
在中医理论指导下，扶正养心方（FZYX）在临床上对治疗缺血性心脏病（IHD）所致心力衰竭（HF）有效。本研究旨在探讨扶正养心方对HF心肌保护作用的机制。利用基因表达综合数据库鉴定IHD亚型的差异基因。通过网络药理学方法，获得扶正养心方活性成分的靶点。我们还通过结扎左冠状动脉前降支构建IHD诱导的HF模型大鼠。采用超声心动图、病理切片染色、酶联免疫吸附测定、蛋白质免疫印迹法、免疫组织化学和定量实时聚合酶链反应分析来验证扶正养心方对心肌的保护作用。我们鉴定出与IHD亚型相关的扶正养心方的53种活性成分和37个潜在靶点。信号转导和转录激活因子3（STAT3）是蛋白质-蛋白质相互作用（PPI）网络中的关键蛋白。通过基因本体论（GO）富集分析鉴定出总共146个生物学过程、10个细胞成分和40个分子功能亚类，并通过京都基因与基因组百科全书（KEGG）富集分析鉴定出包括凋亡在内的18条信号通路。实验表明，扶正养心方显著抑制心肌细胞凋亡，促进STAT3的表达和磷酸化，并改善心脏功能。扶正养心方通过多成分、多靶点和多途径作用改善心脏功能并保护心肌细胞免受损伤，尤其是其在调节STAT3表达和抗凋亡作用方面的可能作用。
