Hemoglobin-based oxygen carriers alleviate early brain injury after subarachnoid hemorrhage in rats by inhibiting ferroptosis
Objective To investigate the protective effect and mechanism of hemoglobin-based oxygen carriers(HBOC)in early brain injury after subarachnoid hemorrhage(SAH).Methods Intravas-cular perforation was used to prepare rat SAH models.A total of 150 adult male SD rats(purchased from Changsha Tianqin Biotechnology Co.,Ltd.)were randomly divided into sham operation group(sham group),SAH group,HBOC group,ferroptosis promoter group(HBOC+erastin group)and protein kinase B inhibitor group(HBOC±MK2206 group)by a numerical random method.Rats in HBOC group were ad-ministered with HBOC via the femoral vein immediately after the operation,while rats in the SAH group were administered with an equal volume of lactated Ringer's solution.SAH score,neurological function score,and brain water content were measured after 24 h of surgery.Neuronal damage was detected by Nissl staining.The corresponding kit was used to measure glutathione(GSH),malondialdehyde(MDA),and iron content in the right temporal lobe brain tissue.The expression of protein kinase B(Akt)pathway proteins and glutathione peroxidase 4(GPX4)were detected using Western blotting.The t-test was used for comparison between groups.Results The neurological function score of the SAH group was lower than that of the HBOC group(12.50±2.48 vs.16.70±0.45,t=3.734,P＜0.05).Nissl staining showed that the normal neuronal cell count in the SAH group was significantly less than that in the sham group and HBOC group[(17.60±2.41)cells/field vs.(50.40±4.39),(27.80±3.35)cells/field,t=14.640,5.532,P＜0.05].Compared with the sham and HBOC groups,the cerebral water content in the SAH group increased[(79.65±0.13)％vs.(79.05±0.27))％,(79.05±0.27)％,t=11.420,4.486,P＜0.05],and GSH decreased significantly(0.43±0.12 vs.0.80±0.07,0.65±0.06,t=6.048,3.793,P＜0.01),MDA increased(4.69±0.85 vs.1.34±0.34,2.14±0.88,t=8.146,4.652,P＜0.01),iron content increased in tissues[(0.02±0.01)mg/g prot vs.(0.11±0.03),(0.05±0.01)mg/g prot,t=7.194,4.496,P＜0.05],phosphorylated Akt(pAkt)/Akt ratio(0.75±0.05 vs.2.19±0.04,2.035±0.04,t=5.855,3.545,P＜0.05)and GPX4 content decreased(0.31±0.01 vs.1.81±0.05,1.28±0.04,t=73.290,55.810,P＜0.05).Conclusion HBOC alleviate early brain injury after SAH by activating the Akt signaling pathway,antioxidative stress,and inhibiting ferroptosis.
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