Effect Of Edaravone On The Expression Of HMGB1 And NF-κB In The Brain Tissue Of Neonatal Rats With Hypoxic-ischemic Brain Injury

Objective:To investigate the effect of Edaravone on the expression of HMGB1 and NF-κB in the brain tissue of neonatal SD rats after hypoxic-ischemic brain injury.Methods:Totally 108 7-day-old newborn SD rats were randomly divided into 3 groups:sham group（group A n=36）,hypoxic-ischemic brain damage（HIBD）group（group B n=36）,and edaravone intervention group（group C n=36）.Firstly,bilaterally ligating and cutting down the left common carotid artery was carried out via midline neck incision under 10%chloral hydrate sedation.Then put it in a hypoxic box（a closed box with a continuous volume fraction of 8%O₂+a volume fraction of 92%N₂gas mixture）for 1.5 hours.The rats of group C were injected intraperitoneally with edaravone immediately after modeling.Later,they received edaravone twice a day at3 mg/kg for 3 days.For group A,the carotid artery was separated but not cut down.Then these rates were allowed to recover for 2 h in normoxic condition,and then returned to their dam.Rats in group A and B were injected with an equal volume of0.9%sodium chloride injection.Rats were sacrificed in batches at 6,12,24,48,72,and 120 h.Cortex tissues were collected for HE staining,immunohistochemical detection of HMGB1 and NF-κB expression,and TUNEL detection to measure cell apoptosis.Results:The expression of HMGB1 and NF-κB was observed in the cerebral cortex of rats in the 6h group.At 24h after hypoxic-ischemia,the number of positive cells in the cerebral cortex of HMGB1 reached the peak.Compared with the 6h,12h,48h,72h,and 120h groups,there was a significant difference in the number of positive cells in the 24h group（P<0.05）;the number of NF-κB positive cells in the 24h group was higher than that of 6h,12h,48h,72h,120h,and there was a significant difference between them（P<0.05）.At the same time,compared with group A,the expression of HMGB1 and NF-κB in the cerebral cortex of group B and group C were significantly increased（P<0.05）.The number of positive cells of HMGB1 and NF-κB in rat cerebral cortex in group C was less than that in group B,and the difference was statistically significant（P<0.05）;6h after hypoxia-ischemia,apoptotic cells in group B and C can be observed in the cerebral cortex of rats,and the number of apoptotic cells reaches a peak in 24 hours.There was a significant difference between the group B and group A of the number of apoptotic cells in the cerebral cortex of rats.Similarly,there was a significant difference between the group C and group A of the number of apoptotic cells in the cerebral cortex of rats（P<0.05）.Conclusion:1.In neonatal rats after hypoxia-ischemia,the expressions of HMGB1 and NF-κB in the cerebral cortex were increased,and the trend of apoptotic cells is related to HMGB1.It is speculated that the apoptosis of neurons may be related to the release of HMGB1 and NF-κB.2.The intervention of edaravone can alleviate the pathological changes in the brain tissue of newborn rats after hypoxic-ischemic injury.The mechanism may be related to the decreased expression of HMGB1 and NF-κB in neurons,thereby reducing neuronal apoptosis,which may play a significant role in brain protection in certain degree.