基于生物信息学的通心络胶囊治疗急性心肌梗死的研究

doi:10.5246/jcps.2024.11.075

中国药学(英文版) ›› 2024, Vol. 33 ›› Issue (11): 1040-1057.DOI: 10.5246/jcps.2024.11.075

基于生物信息学的通心络胶囊治疗急性心肌梗死的研究

苏靖靖¹, 苏康康², 宋艳平¹, 郝丽慧³, 王杏⁴, 杨林泉⁴, 王超⁴, 陈淑霞²^,^*(), 谷剑²^,^*()

^1. 河北医科大学研究生院, 河北石家庄 050017
^2. 河北省人民医院心内三科, 河北石家庄 050051
^3. 河北北方学院研究生院, 河北张家口 075000
^4. 河北省人民医院临床医学研究中心/河北省代谢病重点实验室, 河北石家庄 050051

收稿日期:2024-02-16 修回日期:2024-04-06 接受日期:2024-05-08 出版日期:2024-12-10 发布日期:2024-12-10
通讯作者: 陈淑霞, 谷剑

Bioinformatics-based investigation of the therapeutic potential of Tongxinluo capsule in acute myocardial infarction

Jingjing Su¹, Kangkang Su², Yanping Song¹, Lihui Hao³, Xing Wang⁴, Linquan Yang⁴, Chao Wang⁴, Shuxia Chen²^,^*(), Jian Gu²^,^*()

¹ Graduate School of Hebei Medical University, Hebei 050017, Shijiazhuang, China
² Department of Heart Center, Hebei General Hospital, Hebei 050051, Shijiazhuang, China
³ Graduate School of Hebei North University, Hebei 075000, Zhangjiakou, China
⁴ Hebei Key Laboratory of Metabolic Diseases, Clinical Medical Research Center, Hebei General Hospital, Hebei 050051, Shijiazhuang, China

Received:2024-02-16 Revised:2024-04-06 Accepted:2024-05-08 Online:2024-12-10 Published:2024-12-10
Contact: Shuxia Chen, Jian Gu

摘要/Abstract

摘要：

急性心肌梗死(AMI)预后不良。通心络胶囊(TXL)是目前备受关注的中成药之一。本研究旨在探索通心络胶囊对AMI患者的潜在药理价值, 并寻找相关的免疫靶点。在GSE66360数据集中, 确定了172个高表达基因和16个低表达基因, 利用TCMSP和HERB数据库筛选出803个TXL的关键靶点, 并利用Venn图获得两者的交集基因。基因本体(GO)和京都基因组与基因组百科全书(KEGG)富集分析显示, 这些基因主要与NF-kappa B信号通路、TNF信号通路、IL-17信号通路和其他信号通路相关。用"Cibersort"比较了AMI和对照样本的免疫浸润水平差异, 并采用spearman秩相关分析了免疫细胞与交集基因的相关性。发现肥大细胞活化和中性粒细胞参与了TXL治疗AMI的病理机制。结合"Cibersort"算法, 选择加权基因共表达网络分析(WGCNA)中与22种免疫细胞最显著相关的基因模块进行后续分析。最终, 获得8个Hub基因可作为TXL治疗AMI的潜在新型分子标记。免疫细胞浸润对TXL治疗AMI有重要影响。本研究增加了我们对TXL药理机制的了解, 为开发新的AMI治疗靶点提供了新的思路。

关键词: 生物信息学, 急性心肌梗死, 免疫渗透, 中成药

Abstract:

Acute myocardial infarction (AMI) is associated with a challenging prognosis. Notably, the Tongxinluo capsule (TXL), a proprietary Chinese medicine, has garnered attention for its potential therapeutic effects. This study aimed to elucidate the concealed pharmacological benefits of TXL in AMI patients and identify pertinent immunological targets. In the GSE66360 dataset, 172 upregulated genes and 16 downregulated genes were discerned. Subsequently, 803 key targets of TXL were meticulously sifted through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Herbal Ingredients’ Targets (HERB) databases. The intersection of these datasets was determined using Venn diagrams. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses unveiled that these genes were predominantly associated with the NF-kappa B signaling pathway, TNF signaling pathway, IL-17 signaling pathway, and other signaling cascades. The extent of immune infiltration between AMI and control samples was assessed using Cibersort, and Spearman’s rank correlation was employed to explore the relationship between immune cells and the amalgamated genes. This investigation revealed that the amelioration of AMI with TXL might be linked to an augmentation in mast cell-activated cells and neutrophil invasion. The Weighted Gene Co-expression Network Analysis (WGCNA) identified gene modules strongly correlated with 22 immune cells. These modules were further scrutinized using the Cibersort algorithm, leading to the recognition of eight genes deemed pivotal as potential novel molecular markers for TXL treatment of AMI. The infiltration of defense cells was also found to exert a significant impact. This study contributed to our understanding of the pharmacological mechanisms of TXL and provided valuable insights for future investigations into potential targets for AMI immunotherapy.

Key words: one, Bioinformatics, Acute myocardial infarction, Immune infiltration, Proprietary Chinese medicine

Supporting:

苏靖靖, 苏康康, 宋艳平, 郝丽慧, 王杏, 杨林泉, 王超, 陈淑霞, 谷剑. 基于生物信息学的通心络胶囊治疗急性心肌梗死的研究[J]. 中国药学(英文版), 2024, 33(11): 1040-1057.

Jingjing Su, Kangkang Su, Yanping Song, Lihui Hao, Xing Wang, Linquan Yang, Chao Wang, Shuxia Chen, Jian Gu. Bioinformatics-based investigation of the therapeutic potential of Tongxinluo capsule in acute myocardial infarction[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(11): 1040-1057.

图/表 9

Figure 1. (A) Volcano diagram shows the DEGs in Control and AMI groups using the Xiantao Website. (B) The Heatmap shows the first 50 DEGs in the AMI and Control group using the Xiantao Website. (C) Venn diagram of intersection targets of TXL-related DEGs using the Xiantao Website. (D) PPI network. Nodes represent different proteins. Edges represent protein-protein associations, and the line thickness indicates the strength of data support.

Figure 2. The enrichment pathway analysis of TXL-related DEGs. (A) The significant GO enriched by TXL-related DEGs using the Xiantao Website. (B) The pathways network of the hub genes using the Xiantao Website. (C) The GO enrichment pathway analysis of TXL-related DEGs using WebGestalt.

Figure 3. The GSEA of TXL-related DEGs using the WebGestalt.

Figure 4. (A) The immune cell score for GSE66360 was estimated by CIBERSORT and visualized using the Xiantao Website. (B) Heatmap of the composition of 22 types of immune cells across samples. "ns" means P ≥ 0.05. *P < 0.05, **P < 0.01, and ***P < 0.001.

Figure 5. Relationship between the genes of PLAU, PTGS2, ICAM1, IL1B, GLUL, and MMP9 and immune infiltration.

Figure 6. The association between signature genes and significantly different immune cell infiltration. "N.S." means P ≥ 0.05. *P < 0.05, **P < 0.01, and ***P < 0.001.

Figure 7. (A) Screening with a soft threshold. (B) Dendrogram of all genes clustered based on a dissimilarity measure (1-TOM).

Figure 8. Correlation between infiltration of immune cells and different gene modules.

Figure 9. (A and B) Correlation scatter diagram between green-yellow module genes and phenotypes of immune cell infiltration. (C) Venn map from the two types of screening.

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基于生物信息学的通心络胶囊治疗急性心肌梗死的研究

Bioinformatics-based investigation of the therapeutic potential of Tongxinluo capsule in acute myocardial infarction

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