转录组学分析揭示HMGB1在敌草快中毒肾损伤中的作用机制OA

Objective To investigate the molecular mechanisms of high-mobility group box 1 protein(HMGB1)involvement in diquat(DQ)induced acute kidney injury(AKI)using the public database.Methods Differenti-al gene expression data for diquat poisoning(GSE27170)and HMGB1(GSE18721)were analyzed and down-loaded from the GEO database,with GSE4607 serving as the validation set.Differential genes were subjected to KEGG,GO and PPI analyses.The hub genes were screened using R language.Immune infiltration analysis was performed via the Sangerbox website.Finally,animal experiments were conducted to preliminarily validate the relationship between HMGB1 expression and DQ-induced renal injury.Results Fifty-two hub genes closely relat-ed to immune response,oxidative stress,and metabolic processes were identified.Further screening through the MCC algorithm,PPI network,and independent validation dataset verification yielded four hub genes:NQO1,GCLM,SRXN1,and HMOX1.Immune infiltration and correlation analysis of these four hub genes revealed posi-tive correlations with NK cells and B cells,with particularly higher correlations observed for CD4 T cells and MO macrophages.Finally,animal experiments confirmed that HMGB1 expression plays a critical role in the renal pathological injury induced by DQ poisoning.Conclusion NQO1,GCLM,SRXN1,and HMOX1 are hub genes associated with DQ poisoning and HMGB1,participating in DQ induced AKI by regulating oxidative stress,met-abolic disorders,cellular response to toxins,and immune response pathways.