基于生物信息学探讨中药调节软骨细胞铁死亡干预膝骨性关节炎

Traditional Chinese Medicine Regulating Knee Osteoarthritis by Regulating Iron Death of Chondrocytes Based on Bioinformatics

目的:探索中药调节软骨细胞铁死亡干预膝骨性关节炎的用药规律。方法:通过GEO、FerrDb数据库及Hisat2、DESeq2和R软件获取软骨细胞铁死亡差异靶点并进行富集分析。基于ADME指标及Lipinski规则,通过TCMSP数据库检索差异靶点所对应的化合物和中药,运用cytoscape 3.9.1软件构建潜在靶点、候选化合物及中药的网络,进行网络拓扑分析。对中药性味归经及治疗作用进行统计,分析用药规律。运用AutoDock Vina将核心化合物与关键靶点进行分子对接,评价其对接结合效能。结果:获取60个软骨细胞铁死亡差异靶点,富集分析显示主要通路集中在铁死亡、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)信号通路、破骨细胞分化、白细胞介素-17(interleukin-17,IL-17)信号通路等。其中13个差异靶点可以匹配到化合物,筛选得到993个潜在化合物,386味中药。性味归经统计显示,干预软骨细胞铁死亡的中药寒温并重,以苦、辛、甘味药为主,主要归肝、肺及脾胃经,治疗作用以清热、补虚和活血化瘀为主。分子对接结果显示对接良好,所有结合效能(Affinity)值均<-5.00 kcal·mol^(-1)。结论:本研究发现中药骨碎补、半枝莲、丹参、延胡索等通过多成分、多靶点干预软骨细胞铁死亡,具有较强的调节作用,为深入研究中药干预膝骨性关节炎作用机制中的铁死亡提供了一定的思路与方向。

Objective: To explore the rule of traditional Chinese medicine in regulating chondrocyte ferroptosis in intervening knee osteoarthritis.Methods: The differential targets of chondrocyte ferroptosis were obtained through GEO,FerrDb database and Hisat2,DESeq2 and R software, and enriched and analyzed.Based on the ADME index and Lipinski rule, the compounds and traditional Chinese medicines corresponding to the different targets are retrieved through the TCMSP database, and the network of potential targets, candidate compounds and traditional Chinese medicines is constructed by using the software cytoscape 3.9.1,and the network topology is analyzed.Statistics were made on the nature, taste, meridian tropism and therapeutic effects of traditional Chinese medicine, and drug use laws were analyzed.AutoDock Vina is used to dock core compounds with key targets and evaluate their docking and binding efficiency.Results: 60 different targets of chondrocyte ferroptosis were obtained.Enrichment analysis showed that the main pathways were ferroptosis, hypoxia-inducible factor-1(HIF-1) signal pathway, osteoclast differentiation, interleukin-17(IL-17) signal pathway, etc.Among them, 13 differential targets can be matched with compounds, and 993 potential compounds and 386 Chinese herbal medicines can be screened.According to the statistics of sexual taste and meridian tropism, the traditional Chinese medicines that interfere with the ferroptosis of chondrocytes is both cold or warm in character, mainly bitter, pungent and sweet in flavor, and mainly belongs to the Liver, Lung as well as Spleen and Stomach meridians.The therapeutic effect is mainly to clear heat, replenish deficiency and promote blood circulation and remove blood stasis.The molecular docking results suggest that the docking is good, and all the affinity values are less than-5.00 kcal·mol^(-1).Conclusion: It was found that the traditional Chinese medicines such as Gusuibu(drynaria rhizome),Banzhilian(scutellaria barbata),Danshen(salvia miltiorrhiza) and Yanhusuo(corydalis tuber) have a strong regulatory effect on the ferroptosis of chondrocytes through multi-component and multi-target intervention, which provides a certain idea and direction for the in-depth study of the intervention of traditional Chinese medicine on the ferroptosis of knee osteoarthritis.