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白藜芦醇通过基于网络药理学和分子对接的多靶点抗凋亡机制改善脂多糖诱导的模型中的突发性感音神经性听力损失。

Resveratrol Ameliorates Lipopolysaccharide-Induced Sudden Sensorineural Hearing Loss in Model through Multitarget Antiapoptotic Mechanism Based on Network Pharmacology and Molecular Docking.

作者信息

Ye Shiming, Liu Jing, Dong Qi, Wang Xinxin

机构信息

Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, China.

Department of Otolaryngology, Yizheng People's Hospital, Yangzhou 211400, Jiangsu, China.

出版信息

Evid Based Complement Alternat Med. 2022 May 19;2022:6404588. doi: 10.1155/2022/6404588. eCollection 2022.

Abstract

OBJECTIVE

To explore the effects of resveratrol (RSV) on hair cell apoptosis caused by sudden sensorineural hearing loss (SSNHL) and its effect on lipopolysaccharide-induced apoptosis of HEI-OC1 cells.

METHODS

We used the network pharmacology method to screen molecules related to RSV for the treatment of SSNHL and analyzed these molecules and their enriched biological processes and signaling pathways through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. We selected hub genes related to apoptosis using protein-protein interaction (PPI) analysis for and molecular docking verification.

RESULTS

Eighty overlapping genes were identified as potential targets for RSV treatment of SSNHL. Further GO analysis showed that the biological processes were mainly related to toxicity, cell proliferation, and lipopolysaccharide reactions. KEGG analysis showed that the AGE-RAGE signaling pathway in diabetic complications, Kaposi's sarcoma-associated herpesvirus infection, FoxO signaling pathway, PI3K-Akt signaling pathway, and other inflammatory signaling pathways were concentrated. , and were screened as HUB genes using PPI analysis. The apoptosis-related proteins TNF, CASP3, AKT1, and TP53 were selected for experiments, which showed that mRNA was significantly different before and after RSV intervention, confirming that the corresponding protein receptors could bind well with RSV.

CONCLUSION

RSV mainly affects the prognosis of SSNHL through anti-inflammatory effects and may improve hair cell apoptosis caused by inflammatory factors through multitargeted interventions involving TNF, CASP3, AKT1, and TP53.

摘要

目的

探讨白藜芦醇(RSV)对突发性感音神经性听力损失(SSNHL)所致毛细胞凋亡的影响及其对脂多糖诱导的HEI-OC1细胞凋亡的作用。

方法

采用网络药理学方法筛选与RSV治疗SSNHL相关的分子,并通过京都基因与基因组百科全书(KEGG)和基因本体论(GO)分析对这些分子及其富集的生物学过程和信号通路进行分析。利用蛋白质-蛋白质相互作用(PPI)分析筛选与凋亡相关的枢纽基因并进行分子对接验证。

结果

确定了80个重叠基因作为RSV治疗SSNHL的潜在靶点。进一步的GO分析表明,生物学过程主要与毒性、细胞增殖和脂多糖反应有关。KEGG分析表明,糖尿病并发症中的AGE-RAGE信号通路、卡波西肉瘤相关疱疹病毒感染、FoxO信号通路、PI3K-Akt信号通路等炎症信号通路富集。通过PPI分析筛选出 、 和 作为枢纽基因。选择凋亡相关蛋白TNF、CASP3、AKT1和TP53进行 实验,结果显示RSV干预前后mRNA有显著差异,证实相应的蛋白受体可与RSV良好结合。

结论

RSV主要通过抗炎作用影响SSNHL的预后,并可能通过涉及TNF、CASP3、AKT1和TP53的多靶点干预改善炎症因子所致的毛细胞凋亡。

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