基于WGCNA探讨葛根素对呕吐毒素诱导C6细胞损伤的保护作用

Exploring the Protective Effect of Puerarin on Deoxynivalenol-induced C6 Cell Injury Based on WGCNA

【目的】利用呕吐毒素(deoxynivalenol,DON)构建C6细胞损伤模型,分析葛根素(puerarin,PUE)对DON诱导C6细胞损伤的保护作用机制。【方法】通过RNA测序(RNA-seq)和加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA),挖掘与PUE缓解DON诱导C6细胞损伤最相关的关键模块和关键核心靶点基因,探究PUE缓解DON诱导的神经毒性作用的分子机制。【结果】PUE可以显著抑制DON诱导的C6细胞活力下降,对损伤的C6细胞形态有所恢复,可有效缓解DON诱导的C6细胞损伤。RNA-seq和WGCNA结果表明,Blue模块是与PUE缓解DON诱导C6细胞损伤表型最相关的关键模块,从中筛选出S100a11、Pdia3、Hsp90b1等基因是PUE发挥对DON诱导C6细胞损伤保护作用的关键核心基因。【结论】PUE可能是通过靶向关键核心基因参与内质网中的蛋白质加工途径从而缓解DON诱导的C6细胞损伤。

【Objective】The experiment used deoxynivalenol(DON)to construct a C6 cell injury model and analyzed the protective mechanism of puerarin(PUE)in alleviating DON-induced C6 cell injury.【Method】By using RNA sequencing(RNA-seq)and weighted gene co expression network analysis(WGCNA),we aimed to identify the key modules and core target genes,which was most closely related to the alleviation of PUE on DON-induced C6 cell injury.Furthermore,we explored the molecular mechanism of PUE in alleviating DON-induced neurotoxicity.【Result】The PUE significantly inhibited the decrease in the cell viability induced by DON,restored the morphology of damaged C6 cells,and effectively alleviated DON-induced cytotoxicity.The RNA seq and WGCNA results indicated that the Blue module was the most relevant key module to the alleviation of PUE on DON-induced C6 cell injury,and S100a11,Pdia3 and Hsp90b1 genes were selected as the key core genes.【Conclusion】These results suggest that PUE may alleviate DON-induced C6 cell injury by targeting key core genes and regulating in endoplasmic reticulum signaling pathway.