Mechanism of MAPK Signaling in Microglia Responses After Alcoholic Brain Injury

CUI Rongyan; MA Chunyu

doi:10.3969/j.issn.2096-305X.2025.03.005

Abstract：Objective To explore the mechanism of MAPK signaling in mediating inflammation after alcoholic brain injury and to clarify the pathogenesis of alcoholic brain injury.Methods 33 male SPF grade Wistar rats were selected as the research subjects.The rats were divided into the control group,the model group and the intervention group by the random number table method.The control group was given normal feeding,while the model group was given 30%ethanol by gavage every day for the first two weeks at a dose of 10 mL/(kg·d),and 50%ethanol by gavage every day for the following four weeks.The dose was 12 mL/(kg·d).In the intervention group,on the basis of the model group,5 μL of SB202190 solution with a concentration of 10 μmol/L was injected into the lateral ventricle one day before modeling,at the end of the second week of modeling,and at the end of the sixth week of modeling,respectively.The degree of neurological function impairment in alcohol-exposed rats was evaluated by the modified neurological severity score(MNSS),the morris water maze test(MWMT),and brain tissue hematoxylin-eosin(HE)staining.The serum concentration changes of inflammatory factors TNF-α,NF-κB,IL-1 and IL-10 were quantified by enzyme-linked immunosorbent assay(ELISA),and the activation level of microglia was detected by immunofluorescence staining.Western Blot was used to determine the protein expression of MAPK pathway molecules p-p38 MAPK,p-JNK and p-ERK in brain tissue.Results There were statistically significant differences in the performance of rats in the control group,model group and intervention group in the MNSS and MWMT tests(P<0.05).The brain injury of rats in the model group was obvious,and it improved in the intervention group.HE staining of the brain tissue in the hippocampus showed that the cell structure in the model group was disordered and the neurons were damaged,while the lesions in the intervention group were alleviated.The expression levels of TNF-α,NF-κB,IL-1 and IL-10 in the brain tissue of rats in the model group and the fluorescence signal intensity of Iba-1+microglia were enhanced(P<0.05).The results of the Western Blot experiment showed that the protein expressions of p-p38 MAPK,p-JNK and p-ERK in the model group were upregulated,while the expressions were downregulated after the intervention of p38 MAPK inhibitor(P<0.05).Conclusion There is a significant correlation between the MAPK signaling pathway and alcoholic brain injury.By inhibiting the MAPK signaling pathway,the increase of inflammatory factors in brain tissue caused by alcoholic brain injury can be suppressed,and the pathological changes of brain tissue injury and the neurological functional status of alcoholic brain injury can be improved.