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| 基于网络药理学和实验验证探究通窍活血汤通过BCL2/GABRA1/SCN5A通路干预突发性聋的研究 |
| Investigation of the Intervention of Tougao Huoxue Decoction on Sudden Deafness through the BCL2/GABRA1/SCN5A Pathway Based on Network Pharmacology and Experimental Validation |
| 投稿时间：2025-11-23 修订日期：2026-03-28 |
| DOI： |
| 中文关键词: 通窍活血汤、网络药理学、动物实验、BCL2、GABRA1、SCN5A |
| 英文关键词:Tongqiao huo xue Decoction, Network Pharmacology, Animal Experiment, BCL2, GABRA1, SCN5A |
| 基金项目:浙江省中医药科技计划项目（No.2023ZR096 2023ZF106） |
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| 中文摘要: |
| 目的：基于网络药理学和实验验证，探讨通窍活血汤治疗突发性聋的作用机制。方法：通过TCMSP数据库收集通窍活血汤活性成分及靶点，GeneCards数据库获取突发性聋靶点，Venny软件取交集靶点，Cytoscape软件构建网络图，string数据库构建PPI网络图，David数据库进行GO/KEGG富集分析，获取核心基因BCL2/GABRA1/SCN5A，选取SPF级小鼠，通过改良小承气汤加饥饱失常法及光化学反应法造模，分为生理盐水灌胃组、通窍活血汤灌胃组、通窍活血汤鼻腔给药组、生理盐水滴鼻组，连续给药2周，处死小鼠后取耳蜗组织进行HE染色及WB法检测BCL2、GABRA1、SCN5A蛋白表达。结果：本研究获得通窍活血汤活性成分237个，与突发性聋靶点交集基因196个，PPI网络图锁定研究靶基因为BCL2、GABRA1、SCN5A，GO功能富集分析获得BP、CC、MF相关条目，KEGG通路分析得出相关通路 ；WB法检测结果显示不同组别间BCL2、GABRA1、SCN5A蛋白表达及免疫荧光强度差异无统计学意义通窍活血汤灌胃组与生理盐水滴鼻组（P=0.016）、生理盐水灌胃组（P=0.000）、通窍活血汤滴鼻组（P=0.031）ABR反应阈存在统计学差异。（结论：通窍灌胃组治疗突发性聋有一定的临床疗效，但其确切作用机制仍需进一步研究。 |
| 英文摘要: |
| Objective: To explore the therapeutic mechanism of Tougao Huoxue Decoction in treating sudden deafness based on network pharmacology and experimental validation. Methods: The active ingredients and targets of Tougao Huoxue Decoction were collected through the TCMSP database. Targets related to sudden deafness were obtained from the GeneCards database. The intersection targets were obtained using Venny software. Cytoscape software was used to construct network diagrams. The PPI network diagram was constructed using the STRING database. GO/KEGG enrichment analysis was performed using the DAVID database to obtain the core genes BCL2/GABRA1/SCN5A. SPF-grade mice were selected and models were established through the modified Xiao Chengqi Decoction combined with irregular feeding and photochemical reaction methods. The mice were divided into four groups: saline gavage group, Tougao Huoxue Decoction gavage group, Tougao Huoxue Decoction nasal administration group, and saline nasal drop group. The administration was continued for two weeks. After sacrificing the mice, the cochlear tissues were taken for HE staining and WB detection of BCL2, GABRA1, and SCN5A protein expression. Results: A total of 237 active ingredients of Tougao Huoxue Decoction were obtained, and 196 intersection genes with targets related to sudden deafness were identified. The PPI network diagram identified the research target genes as BCL2, GABRA1, and SCN5A. GO function enrichment analysis obtained BP, CC, and MF related items, and KEGG pathway analysis identified related pathways. The Western blot (WB) assay results showed no statistically significant differences in protein expression levels and immunofluorescence intensity of BCL2, GABRA1, and SCN5A among the different groups. However, significant differences in Auditory Brainstem Response (ABR) thresholds were observed between the Tongqiao Huoxue Decoction gavage group and the normal saline intranasal administration group (P=0.016), normal saline gavage group (P=0.000), and Tongqiao Huoxue Decoction intranasal administration group (P=0.031). (Conclusion: The Tongqiao Huoxue Decoction gavage group demonstrated certain clinical efficacy in treating sudden sensorineural hearing loss, though its exact mechanism of action requires further investigation.) |
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