槲皮素通过抑制细胞凋亡减轻脊髓损伤

Quercetin Alleviates Spinal Cord Injury by Inhibiting Apoptosis H

目的:研究并验证槲皮素治疗脊髓损伤(SCI)的疗效及可能的作用机制。方法:通过网络药理学方法,检索中药系统药理数据库和分析平台(TCMSP)数据库、GeneCards、DisGeNET数据库及OMIM数据库,筛选槲皮素治疗SCI的相关靶点,构建Venn图,得到槲皮素-SCI关键靶点,进一步将关键靶点基因输入STRING数据库,构建蛋白质-蛋白质相互作用网络(PPI)。将关键靶基因输入Metascape数据库进行GO及KEGG富集分析。使用AutodockTools软件进行分子对接。最后通过体外细胞试验进行验证。结果:通过筛选,共得到259个槲皮素-SCI关键靶点;通过度值、中介中心度及接近中心度值筛选,最终纳入了槲皮素作用于SCI的关键靶基因10个,分别为AKT1、VEGFA及TP53等基因。槲皮素可以与靶点蛋白AKT1、VEGFA和TP53自发结合。GO生物学过程分析结果表明,槲皮素可能通过凋亡信号通路参与治疗SCI。体外细胞试验结果表明,槲皮素通过抑制细胞凋亡增加双氧水(H2O2)处理的PCP12细胞的细胞活力。结论:槲皮素可能通过抑制细胞凋亡治疗SCI,提示槲皮素对治疗SCI可能有一定的应用前景。

Objective:To investigate and validate the efficacy and possible mechanisms of quercetin in treating spinal cord injury(SCI).Methods:Using network pharmacology methods,we screened relevant targets of quercetin treatment for SCI from TCMSP databases,GeneCards,DisGeNET databases and OMIM databases,constructed Venn diagrams,obtained key targets of quercetin-SCI,further inputted the key target genes into STRING database to construct protein-protein interaction networks(PPI).We inputted the key target genes into Metascape database for GO and KEGG enrichment analysis.We conducted molecular docking using AutodockTools software.Finally,we validated the results through in vitro cell experiments.Results:After screening,a total of 259 quercetin-SCI key targets were obtained.Through degree value,medium centrality and closeness centrality value screening,we finally selected 10 key target genes of quercetin acting on SCI,including AKT1,VEGFA and TP53 genes.Quercetin can spontaneously bind with target proteins AKT1,VEGFA and TP53.GO biological process analysis showed that quercetin may participate in treating SCI through apoptosis signaling pathways.Cell experiment results showed that quercetin increased the cell viability of PCP12 cells treated with H2O2 by inhibiting apoptosis.Conclusion:Quercetin may treat SCI by inhibiting apoptosis,suggesting that it may have potential application prospects for treating SCI.