温阳复元方调控CTR 1/FDX 1信号通路改善脑缺血再灌注损伤大鼠神经元铜死亡的机制研究OA

Objective To investigate the mechanism of Wenyang Fuyuan Formula(温阳复元方,WYFYF)on neuronal cuproptosis in rats with cerebral ischemia-reperfusion injury(CIRI).Methods SD rats were divided into sham operation group,model group,copper ion chelating agent group,and WYFYF low/medium/high-dose groups.The middle cerebral artery occlusion/reperfusion(MCAO/R)model was established.The sham operation and model groups received 0.9％sodium chloride solution by gavage,while the WYFYF low/medium/high-dose groups received 1.5,3,and 6 mL of WYFYF by gavage,respectively,once daily for 7 consecutive days.After model establishment,TTC staining,neurological deficit score,and levels of Cu2+and glutathione(GSH)were compared.HE and Nissl staining were performed to observe the pathological morphological changes of brain tissue.Immunohistochemistry(IHC),qRT-PCR,and Western blot(WB)were used to detect the mRNA and protein expression of DLAT,FDX1,LIAS,and CTR1.Results Compared with the sham operation group,the model group showed a significantly increased neurological deficit score,obvious white infarct areas,severe neuronal damage,decreased Nissl bodies,reduced GSH content,upregulation of CTR1 and DLAT,and downregulation of FDX1 and LIAS(all P<0.05).Compared with the model group,after intervention with copper ion chelating agent and WYFYF,neurological deficits were significantly alleviated,pathological injury of brain tissue was mitigated,surviving neurons and Nissl bodies increased,GSH content was elevated,CTR1 and DLAT expression were downregulated,and FDX1 and LIAS expression were upregulated(all P<0.05).Conclusion WYFYF can regulate cuproptosis in neuronal cells of CIRI rats,and the mechanism may involve inhibition of the CTR1/FDX1 pathway.