Association between hippocampal ferroptosis and emotional disorders induced by neuropathic pain in rats with chronic constriction injury
10.13406/j.cnki.cyxb.003826
- VernacularTitle:探究CCI大鼠海马铁死亡与神经病理性疼痛诱发情绪紊乱的相关性分析
- Author:
Yanan LI
1
;
Chunchun XUE
;
Kaiqiang WANG
Author Information
1. 上海中医药大学附属市中医医院疼痛科,上海 200071
- Keywords:
neuropathic pain;
ferroptosis;
hippocampus;
ferrostatin-1;
erastin
- From:
Journal of Chongqing Medical University
2025;50(5):630-639
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the phenomenon of hippocampal ferroptosis and its change in a rat model of chronic constriction injury(CCI)of the sciatic nerve,as well as the association between hippocampal ferroptosis and emotional disorders induced by neuro-pathic pain.Methods:A total of 32 male Sprague-Dawley rats were randomly divided into Sham group,CCI group,CCI+F group,and CCI+E group,with 8 rats in each group.The rats in the CCI+F group and the CCI+E group were given intraperitoneal injection of Ferrostatin-1(10 mg/kg)and Erastin(10 mg/kg),respectively,since day 7 after surgery for two consecutive days.Mechanical with-drawal threshold(MWT),paw withdrawal latency(PWL),and open field test(OFT)were measured before surgery and on days 7 and 14 after surgery.On day 14 after surgery,the rats were sacrificed to col-lect hippocampal tissue;Western blot was used to measure the levels of GPX4,xCT,and FTH1;related kits were used to measure the expression levels of MDA and GSH;HE staining,Nissl staining,and immunofluorescent staining were performed;transmission electron microscopy was used to observe the structural changes of the mito-chondria.Results:In terms of behavioristics,compared with the Sham group,the CCI group had significant reductions in MWT and PWL on day 7 after surgery(P<0.001),with further reductions from day 7 to day 14 after surgery(P<0.001);compared with the CCI group,the CCI+F group had significant increases in MWT and PWL on day 14 after surgery(P<0.001),and the CCI+E group had no significant change in MWT and a significant reduction in PWL(P<0.01).In terms of the OFT test,compared with the Sham group,the CCI group had significant reductions in total distance and number of central squares crossed(P<0.001)and a significant increase in immobility time(P<0.001);compared with the CCI group,the CCI+F group had significant increases in total distance and number of central squares crossed and a significant reduction in immobility time,while the CCI+E group had no significant changes in these indi-ces.In terms of biochemical results,compared with the Sham group,the CCI group had significant reductions in GPX4,xCT,and FTH1(P<0.01),a significant increase in MDA,and a significant reduction in GSH;compared with the CCI group,the CCI+F group had sig-nificant increases in GPX4,xCT,and FTH1(P<0.05),a significant reduction in MDA(P<0.001),and a significant increase in GSH(P<0.01),and the CCI+E group had significant reductions in xCT and FTH1,with no significant changes in MDA and GSH.In terms of morphology,compared with the Sham group,the CCI group had damage and necrosis of hippocampal neurons,significant reductions in Nissl bodies and c-Fos level(P<0.05),and significantly damaged mitochondrial cristae on day 14 after surgery;compared with the CCI group,the CCI+F group had intact structures of hippocampal neurons,significant increases in Nissl bodies and c-Fos(P<0.05),and relatively intact mitochondria,while there were no significant differences in c-Fos and Nissl bodies between the CCI+E group and the CCI group.The pairwise linear correlation analysis of PWL,MWT,GPX4,OFT,and c-Fos on day 14 after surgery showed a signifi-cantly positive correlation between any two indicators(P<0.01).Conclusion:Peripheral nerve injury triggers ferroptosis in the hippo-campus and causes anxiety and depression,thereby aggravating ferroptosis and accelerating the development of central hyperalgesia.
