Analysis of differential gene expression profiles uncovers mechanisms of Xuesaitong injection against cerebral ischemia-reperfusion injury

被引：9
作者：
Zhang, Ying [1 ]
Zhang, Tiejun [2 ]
Jia, Jing [3 ]
Jin, Chaohui [1 ]
Li, Yuwen [1 ]
机构：
[1] Sichuan Univ, West China Hosp, Dept Pharm, 37 Guoxue Alley, Chengdu 610041, Peoples R China
[2] Sichuan Univ, West China Hosp, Dept Neurosurg, Chengdu 610041, Peoples R China
[3] Shandong Univ Tradit Chinese Med, Affiliated Hosp, Dept Pharm, Jinan 250014, Peoples R China
来源：
PHYTOMEDICINE | 2022年 / 103卷
基金：
中国国家自然科学基金; 国家重点研发计划;
关键词：
Xuesaitong injection; Panax notoginseng saponins; Neuroprotective effects; BDNF; Bioinformatics analyses; REDUCES INFARCT SIZE; NEUROTROPHIC FACTOR; SIGNALING PATHWAY; ARTERY OCCLUSION; GROWTH-FACTOR; BRAIN-INJURY; STROKE; NEUROGENESIS; BDNF; ONTOLOGY;
D O I：
10.1016/j.phymed.2022.154224
中图分类号：
Q94 [植物学];
学科分类号：
071001 ;
摘要：
Background: Xuesaitong injection (XST), a well-known traditional Chinese patent medicine, has been widely used in the treatment of cardiovascular and cerebrovascular diseases. The exact mechanisms of XST in ischemic stroke remain to be thoroughly elucidated. Purpose: This study aims to characterize the candidate differentially expressed genes (DEGs) and pathways of XST in ischemic stroke by bioinformatics analysis, and to explore new clues for the underlying mechanisms of XST. Methods: A dataset (GSE61616) was performed to screen out DEGs for deep analysis. Series Test of Cluster analysis for DEGs was carried out. For all DEGs, Gene Ontology (GO) annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for visualization. The screened hub gene expression characteristics were verified in middle cerebral artery occlusion (MCAO) rats. In vivo studies have demonstrated the mechanisms of XST against cerebral ischemia-reperfusion (CIR) injury. Results: A total of 8066 DEGs were screened out and the expression of genes in profile 8 was suggested to have clinical significance. The MAPK signaling pathway was indicated as the most significantly enriched pathway in profile 8. Bdnf was identified as the most significant hub gene according to node degree. Animal experiments demonstrated that XST attenuated CIR injury. XST increased brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase B (TrkB) levels in MCAO. Furthermore, the knockdown of BDNF by siRNA abolished the in vivo effects of XST on brain injury, neurodegeneration and apoptosis after CIR. Conclusion: The integrated strategy, based on bioinformatics analyses with experimental verification, provides a novel cellular mechanism by which XST alleviates CIR injury. The BDNF-TrkB pathway was highly thought to play a vital role in the neuroprotective effects of XST.
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页数：11
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