基于生物信息学探讨精索静脉曲张相关性男性不育症与铁死亡相关的关键基因及潜在中药预测

Exploring Ferroptosis-Related Key Genes Associated with Varicocele-Associated Male Infertility and Predicting Potential Traditional Chinese Medicines Based on Bioinformatics

目的利用生物信息学分析和识别精索静脉曲张(Varicocele,VC)相关性男性不育症与铁死亡相关的关键基因,并预测潜在治疗作用的中药。方法通过GEO、FerrDb、Genecards数据库及R软件获得VC相关性不育铁死亡的关键差异基因,并对关键基因进行富集分析。利用TCMSP数据库、HERB数据库检索关键基因对应的中药和化合物,运用Cytoscape 3.7.1软件构建关键基因-中药-化合物网络,并对网络进行拓扑分析。对纳入的中药进行性味归经统计,并分析用药规律。运用AutoDock Tools软件对核心化合物和关键靶点进行分子对接,并评估对接效能。结果最终获得了6种关键差异基因,富集分析显示主要通路集中在自噬通路、AMPK信号通路、mTOR信号通路、细胞衰老等。根据差异基因共匹配得到41种中药和342种化合物。性味归经统计分析,干预VC相关性男性不育症铁死亡的中药寒温并用,以苦、辛、甘味药为主,主要归肝、肾经,药效以清热利湿、行气活血、补肾填精为主。分子对接结果显示,化合物和关键靶点对接效能较好,对接能均<-4.5 kcal·mol^(-1)。结论通过研究发现枸杞子、杜仲、桑白皮、吴茱萸、鸡血藤等中药通过多成分、多靶点干预VC相关性男性不育症铁死亡,具有较好的调节作用,为后续深入研究中药干预铁死亡机制提供一定的思路和方向。

Objective To analyze and identify key ferroptosis-related genes associated with varicocele(VC)-associated male infertility using bioinformatics and to predict potential therapeutic traditional Chinese medicines(TCM).Methods Key differential genes of ferroptosis in VC-associated infertility were obtained by GEO,FerrDb,and Genecards databases and analyzed using R software.Enrichment analysis of key genes was conducted.The TCMSP and HERB databases were used to search the TCMs and compounds corresponding to the key genes.Cytoscape 3.7.1 software was used to construct a key gene-TCM-compound network,which was then subjected to topological analysis.The medicinal properties meridian of the included TCMs were statistically analyzed,along with an analysis of medication rules.AutoDock Tools software was used for molecular docking between core compounds and key targets,and the docking efficacy was evaluated.Results Six key differential genes were identified.Enrichment analysis showed that the main pathways involved were the autophagy pathway,AMPK signaling pathway,mTOR signaling pathway,and cellular senescence.Based on the differential genes,41 TCMs and 342 compounds were matched.The statistical analysis of the medicinal properties meridian indicated that the TCMs intervening in VC-associated male infertility caused ferroptosis using both cold and warm herbs,mainly with bitter,pungent,and sweet taste,targeting the liver and kidney meridians.The primary therapeutic effects included clearing heat and dampness,promoting Qi and blood,and tonifying the kidney and essence.Molecular docking results showed good docking efficiency between the compounds and key targets,with all docking energies less than-4.5 kcal·mol^(-1).Conclusion This study found that TCMs such as Lycii Fructus,Eucommiae Cortex,Mori Cortex,Euodiae Fructus,and Spatholobi Caulis have good regulatory effects on VC-associated male infertility ferroptosis through multi-component and multi-target interventions.This provided some ideas and directions for further research on the mechanism of TCM intervention in ferroptosis.