Sinomenine inhibits neuronal ferroptosis after traumatic brain injury through the SLC7A11/gluta-thione peroxidase-4 pathway
Objective To explore the effect and mechanism of sinomenine(SIN)on neuronal fer-roptosis caused by traumatic brain injury(TBI)in rats.Methods Rats were randomly divided into sham operation(Sham)group,TBI group,TBI+SIN group,and TBI+SIN+Erastin group.After establishing the model,the experimental group was intraperitoneally injected with SIN every day;SIN+Erastin group was injected with SIN and Erastin every day;the Sham and TBI groups were injected with an equal volume of normal saline intraperitoneally.Three days after TBI,neurological function was evaluated by the neuro-logical severity scores(NSS)rating scale,the expression of NeuN and glutathione peroxidase-4(GPX4)was detected by immunofluorescence,the levels of glutathione(GSH)and malondialdehyde(MDA)were detected by biochemical methods,and the expression of related proteins was detected by Western blotting.The quantitative data were compared using t test.Results The NSS score showed that the score of the TBI+SIN group[(1.80±0.84)points]was lower than that of the TBI group and the TBI+SIN+Erastin group[(3.40±0.89),(3.40±0.55)points],and the difference was statistically significant(t=2.92,3.56,P＜0.05).The GSH content in brain tissue after TBI(0.43±0.11,t=4.62,P＜0.05)was de-creased,while the MDA content(2.88±0.32,t=5.43,P＜0.05)was increased;after SIN treatment,the GSH content(0.73±0.12,t=3.12,P＜0.05)was increased,while the MDA content(1.88±0.33,t=2.88,P＜0.05)was decreased As compared with the TBI+SIN group,the GSH content(0.44±0.15,t=7.15,P＜0.05)was decreased,while the MDA content(2.50±0.26,t=5.12,P＜0.05)was increased after Erastin treatment.The expression of SLC7A11(0.57±0.18,t=3.72,P＜0.05)and GPX4(0.49±0.23,t=5.34,P＜0.05)in brain tissues was decreased after TBI,and SIN treatment increased the expression of SLC7A11(1.13±0.26,t=5.25,P＜0.05)and GPX4(1.63±0.31,t=4.93,P＜0.05).Erastin treatment decreased the expression of SLC7A11(0.52±0.14,t=3.89,P＜0.05)and GPX4(0.64±0.38,t=5.18,P＜0.05).Immunofluorescence staining showed that NeuN(75.40±4.26),the number of NeuN(112.40±8.35,t=7.59,P＜0.05)and GPX4(120.40±8.14,t=9.47,P＜0.01)positive cells increased after SIN treatment.As compared with the TBI+SIN group,the number of NeuN(80.41±7.14,t=10.33,P＜0.05)and GPX4(82.15±4.59,t=11.67,P＜0.01)positive cells decreased in the TBI+SIN+Erastin group.Conclusion SIN improves ferroptosis caused by TBI through the SLC7A11/GPX4 pathway.
NETL
NSTL
万方数据
