骨关节炎中自噬相关基因的鉴定及其靶向中药成分的筛选

Identification of autophagy-related genes in osteoarthritis and screening of targeted Chinese medicine components

关键词:  骨关节炎  自噬相关基因  加权基因共表达网络分析  白藜芦醇  姜黄素

Key words:  osteoarthritis  autophagy-related gene  weighted gene co-expression network analysis  resveratrol  curcumin

摘要:

[目的] 研究旨在鉴定骨关节炎（OA）中的自噬相关基因，并筛选其靶向中药成分。[方法] 从基因表达综合数据库下载微阵列数据集GSE55235和GSE55457进行分析。分别筛选OA样本和健康对照样本之间的差异表达基因。然后分别对GSE55235和GSE55457数据集进行加权基因共表达网络分析，以获取OA中的枢纽基因模块和枢纽基因。将差异表达基因、枢纽基因和自噬相关基因取交集，获得OA中关键的自噬基因。使用微阵列数据集GSE12021验证关键的自噬基因的准确性。针对这些关键基因，筛选了一些中药成分，并进行分子对接验证。[结果] 通过整合两个微阵列数据集中的差异表达基因、枢纽基因和自噬相关基因，最终获得了OA中3个关键的自噬基因。微阵列数据集GSE12021的受试者工作特征曲线验证了关键的自噬基因的准确性。通过筛选靶向中药成分并进行分子对接验证，发现白藜芦醇和姜黄素与这些关键的自噬基因均表现出较强的结合活性。[结论] 研究发现3个可作为OA诊断标志物和治疗靶点的关键自噬基因。此外，白藜芦醇和姜黄素是治疗OA的潜在中药成分。

Abstract:

[Objective] The purpose of this study is to identify autophagy-related genes in osteoarthritis(OA) and to screen targeted traditional Chinese medicine(TCM) ingredients. [Methods] Microarray datasets GSE55235 and GSE55457 were downloaded from the Gene Expression Omnibus database for analysis. Firstly,differentially expressed genes between OA samples and healthy control samples were screened. Then,weighted gene co-expression network analysis was performed on the GSE55235 and GSE55457 datasets separately to obtain the hub gene modules and hub genes in OA. By taking the intersection of differentially expressed genes,hub genes,and autophagy-related genes,key autophagy genes in OA were obtained. The accuracy of the key autophagy genes was validated using the microarray dataset GSE12021. Finally,some TCM ingredients were selected for molecular docking validation of these key genes. [Results] By integrating the differentially expressed genes,hub genes,and autophagy-related genes from the two microarray datasets,three key autophagy genes in OA were ultimately identified. The receiver operating characteristic curve of the microarray dataset GSE12021 validated the accuracy of the key autophagy genes. Through the screening and molecular docking validation of targeted TCM ingredients,it was found that resveratrol and curcumin exhibited strong binding activity with these key autophagy genes. [Conclusion] This study identified three key autophagy genes that can serve as diagnostic markers and therapeutic targets for OA. Furthermore,resveratrol and curcumin are potential Chinese medicine ingredients for the treatment of OA.