Liu Yi, Zhang Yang, Wei Huan, Wang Li, Liao Lishang
Department of Neurosurgery, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China.
Department of Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China.
Sci Rep. 2025 Apr 15;15(1):12861. doi: 10.1038/s41598-025-97642-8.
Subarachnoid hemorrhage (SAH) is a fatal pathological condition in the central nervous system (CNS), characterized by severe clinical consequences. Its treatment remains a significant challenge, especially due to the incomplete understanding of its molecular mechanisms. In this study, we integrated comprehensive bioinformatics analyses with experimental validation to explore the potential pathogenic mechanisms and immune cell infiltration characteristics of SAH, aiming to identify novel diagnostic biomarkers and therapeutic targets. We selected relevant gene expression data from the gene expression omnibus (GEO) database and obtained a gene set associated with SAH from the GeneCards database. Through bioinformatics analysis, we constructed a protein-protein interaction (PPI) network and performed functional enrichment analysis using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases. The analysis revealed 11 key genes and indicated 3 main signaling pathways. Additionally, Drug target prediction and molecular docking analyses revealed that Isorhynchophylline (IRN) exhibits a strong binding affinity to these hub proteins. Importantly, Western blot (WB) experiments confirmed that IRN significantly downregulates the expression of CCL20, IL6, TLR4, and MMP9 in LPS-induced microglial cells, validating its anti-inflammatory effects. In conclusion, our findings not only elucidate the molecular mechanisms underlying SAH but also provide robust bioinformatics and experimental evidence supporting IRN as a promising therapeutic candidate, offering novel insights for future intervention strategies in SAH.
蛛网膜下腔出血（SAH）是中枢神经系统（CNS）中的一种致命病理状况，具有严重的临床后果。其治疗仍然是一项重大挑战，尤其是由于对其分子机制的理解不完整。在本研究中，我们将全面的生物信息学分析与实验验证相结合，以探索SAH的潜在致病机制和免疫细胞浸润特征，旨在识别新的诊断生物标志物和治疗靶点。我们从基因表达综合数据库（GEO）中选择了相关基因表达数据，并从基因卡片数据库中获得了与SAH相关的基因集。通过生物信息学分析，我们构建了蛋白质-蛋白质相互作用（PPI）网络，并使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）数据库进行了功能富集分析。分析揭示了11个关键基因，并指出了3条主要信号通路。此外，药物靶点预测和分子对接分析表明，异钩藤碱（IRN）对这些枢纽蛋白表现出很强的结合亲和力。重要的是，蛋白质免疫印迹（WB）实验证实，IRN在脂多糖诱导的小胶质细胞中显著下调CCL20、IL6、TLR4和MMP9的表达，验证了其抗炎作用。总之，我们的研究结果不仅阐明了SAH的分子机制，还提供了有力的生物信息学和实验证据，支持IRN作为一种有前景的治疗候选药物，为SAH未来的干预策略提供了新的见解。
