Wu Ji, Li Xue-Yu, Liang Jing, Xie Jian, Deng Cheng-Neng, Chen Zhi-Jun, Lai Chang-Sheng, Yang Zhao-Jian
Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Clinical College of Youjiang Medical University for Nationalities, Baise, China.
Ann Transl Med. 2022 May;10(10):567. doi: 10.21037/atm-22-1403.
Intracerebral hemorrhage (ICH) is a type of stroke which results in a high disability and mortality rate and has a poor prognosis. Tongqiao Huoxue Decoction (TQHXD) is a classical Chinese prescription. Clinical practice has proven that TQHXD can promote blood circulation and can effectively treat ICH and its sequelae. However, the current mechanism is still unclear.
The chemical components and target genes of TQHXD were collected from the Traditional Chinese medicine (TCM) Systems Pharmacology and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine analysis platforms, and the gene expression data of ICH tissues were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to obtain differentially co-expressed gene pairs and build a drug-target-disease network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the obtained target genes and shared genes. Finally, molecular docking was carried out to further clarify the utility of TQHXD for the treatment of ICH.
A total of 304 differentially expressed genes in ICH, 42 TQHXD active ingredients, and 279 predicted targets of its active compounds were obtained. Bioinformatics analysis showed that they were involved in angiogenesis, the regulation of wound healing, and other biological processes. Furthermore, their participation in fluid shear stress and the atherosclerosis signaling pathway indicated their close association with the pathological processes of ICH. Finally, molecular docking was carried out to further confirm the tightly binding structural sites of the effective components of TQHXD and key proteins.
In summary, the results of this study suggest that the mechanism of action of TQHXD in the treatment of ICH involves multiple targets and signaling pathways related to its occurrence and development. This study not only provides a new theoretical basis for the treatment of ICH with traditional Chinese medicine, but also provides new ideas for the research and development of drugs for the treatment of ICH.
脑出血(ICH)是一种中风类型,导致高致残率和死亡率,预后较差。通窍活血汤(TQHXD)是一种经典的中药方剂。临床实践证明,通窍活血汤能促进血液循环,有效治疗脑出血及其后遗症。然而,目前其作用机制仍不清楚。
从中药系统药理学和中药分子机制生物信息学分析工具分析平台收集通窍活血汤的化学成分和靶基因,并从基因表达综合数据库(GEO)下载脑出血组织的基因表达数据。进行加权基因共表达网络分析(WGCNA)以获得差异共表达基因对并构建药物-靶标-疾病网络。对获得的靶基因和共享基因进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。最后,进行分子对接以进一步阐明通窍活血汤治疗脑出血的效用。
共获得脑出血中304个差异表达基因、42种通窍活血汤活性成分及其活性化合物的279个预测靶标。生物信息学分析表明,它们参与血管生成、伤口愈合调节等生物学过程。此外,它们参与流体剪切应力和动脉粥样硬化信号通路表明它们与脑出血的病理过程密切相关。最后,进行分子对接以进一步确认通窍活血汤有效成分与关键蛋白的紧密结合结构位点。
总之,本研究结果表明,通窍活血汤治疗脑出血的作用机制涉及与其发生发展相关的多个靶点和信号通路。本研究不仅为中药治疗脑出血提供了新的理论依据,也为脑出血治疗药物的研发提供了新思路。