通络醒脑方调控Nrf2/GPX4信号通路抑制铁死亡对血管性痴呆大鼠认知功能障碍的影响OA

Objective To explore the mechanism of Tongluo Xingnao Decoction on improving cognitive dysfunction in rats with vascular dementia based on the inhibition of ferroptosis based on Nrf2/GPX4 signaling pathway.Methods The rat model of vascular dementia was established.The modeling rats were randomly divided into sham-operation group,model group,agonist group and Tongluo Xingnao Decoction low-and high-dosage groups.After 8 weeks of corresponding interventions,the Morris water maze was used to evaluate the learning and memory abilities of the rats,HE staining and Nissl staining were employed to observe the morphology of neurons in CA1 region of the hippocampus,Prussian blue staining was used to detect Fe3+deposition,colorimetric assays were applied to measure the contents of Fe2+,malondialdehyde(MDA)and GSH in hippocampal tissue,Western blot and RT-qPCR were used to detect the expression of ferroptosis-related proteins Nrf2 and GPX4 in hippocampal tissue.Results Compared with the sham-operation group,the model group showed a significant increase in the escape latency and a significant decrease in the number of original platform crossings(P<0.05),the hippocampal neurons were disordered and decreased in number,with widened intercellular spaces,interstitial edema,Nissl bodies reduced and fragmented,and Fe3+deposition increased significantly,the contents of Fe2+and MDA in hippocampus increased significantly,and the content of GSH decreased significantly(P<0.05),the protein and mRNA expressions of Nrf2 and GPX4 in hippocampus decreased significantly(P<0.05).Compared with the model group,the escape latency of rats in each treatment group was significantly shortened,and the number of crossing the original platform significantly increased(P<0.05),hippocampal neurons were regularly arranged,the number increased,the cell morphology was basically normal,interstitial edema was significantly improved,Nissl bodies increased,Fe3+deposition was significantly reduced,the content of Fe2+,MDA in hippocampal tissue significantly decreased,the content of GSH significantly increased(P<0.05),and the protein and mRNA expressions of Nrf2 and GPX4 in hippocampal tissue significantly increased(P<0.05).Conclusion Tongluo Xingnao Decoction can significantly improve learning and memory impairments as well as hippocampal neuronal damage in vascular dementia model rats,and its mechanism is closely related to activating the Nrf2/GPX4 signaling pathway and inhibiting the ferroptosis process in hippocampal tissue.