Protective effect of 4-hydroxymandelic acid against neuronal cell injury induced by oxygen-glucose deprivation/reoxygenation and brain tissue damage induced by middle cerebral artery occlusion/reperfusion in mice and its mechanism
Objective To investigate the protective effect of 4-hydroxymandelic acid(4-HMA)against neuronal cell inju-ry induced by oxygen-glucose deprivation/reoxygenation(OGD/R)and brain tissue damage induced by middle cerebral artery oc-clusion/reperfusion(MCAO/R)in mice and its mechanism.Methods Primary neuronal cells were extracted and divided into control group(cultured in neuronal culture medium),OGD/R group(treated with OGD/R),and OGD/R+4-HMA group(trea-ted with OGD/R and 4-HMA intervention).After 6 h of cells culture,Western blot was used to measure the levels of protein ki-nase B(Akt)and phosphorylated Akt(p-Akt)in neuronal cells of each group,and CCK-8 assay was used to measure cell viability in each group.C57BL/6 mice were randomly divided into Sham group,MCAO/R group,and MCAO/R+4-HMA group,with 6 mice in each group.The mice in the Sham group were given an external carotid artery stoma alone,but without middle cerebral ar-tery occlusion.The mice in the MCAO/R group and the MCAO/R+4-HMA group were given MCAO surgery,with the restora-tion of blood flow after middle cerebral artery occlusion for 1.5 h;the mice in the MCAO/R+4-HMA group were given intraperito-neal injection of 4-HMA at 0 and 3 h after the restoration of blood flow,while those in the MCAO/R group were not given such treatment.TTC staining was used to measure the percentage of cerebral infarct volume and calculate the percentage of infarct area in total brain volume,and modified Neurological Severity Score(mNSS)was used to assess the behaviors of mice.Results Compared with the control group,the OGD/R group and the OGD/R+4-HMA group had significant increases in the re-lative expression level of p-Akt and p-Akt/Akt ratio(F=10.49,8.87,t LSD=3.02-3.14,P＜0.05),and there was no significant difference in the relative expression level of Akt(P＞0.05).The OGD/R+4-HMA group had a significantly higher cell viability than the OGD/R group(F=104.60,tLSD=7.28,P＜0.05).Compared with the MCAO/R group,the MCAO/R+4-HMA group had significant reductions in mNSS score and the percentage of cerebral infarct volume(F=7.20,108.00,tLSD=3.32,5.41,P＜0.05).Conclusion This study shows that 4-HMA can alleviate neuronal injury caused by OGD/R and reduce the percentage of cerebral infarct volume in MCAO/R mice,possibly by increasing the level of p-Akt in neuronal cells.
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