Therapeutic Effect of Glycyrrhizin on Hypoxic-Ischemic Brain Damage in Neonatal Rats by Regulating Drd2/Cryab/NF-κB Signaling Pathway
Objective:To investigate the therapeutic effect of glycyrrhizin(GL)on hypoxic-ischemic brain damage(HIBD)in neonatal rats by regulating dopamine D2 receptor(Drd2)/α-B crystallin(Cryab)/nuclear factor-KB(NF-κB)signaling pathway.Methods:12 out of 60 neonatal rats at 7d were selected as sham operation group,and the remaining neonatal rats were used to establish the HIBD neonatal rat model by Rice-Vannucci method.36 neonatal rats with successful modeling were divided into HIBD group,GL group and haloperidol group(Drd2 inhibitor)by random number table method,with 12 rats in each group.The neurological deficit score and brain water content of neonatal rats in each group were measured.The pathological changes of hippocampus were observed by hematoxylin-eosin staining(HE)and Nissl staining.Neuronal apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)staining.The levels of tumor necrosis factor(TNF-α)and interleukin-6(IL-6)in serum were detected by enzyme-linked immunosorbent assay(ELISA).The expression of Drd2/Cryab/NF-KB pathway protein in hippocampus was detected by Western blot.Results:Compared with sham operation group,the structure of hippocampal CA1 in HIBD group was blurred,the arrangement of neurons was disordered,the number of Nissl bodies was decreased,the neurological deficit score,brain water content,neuronal apoptosis rate,TNF-α,IL-6,p-NF-κB/NF-κB protein expression were increased,and the expression of Drd2 and Cryab protein was decreased(P<0.05).Compared with HIBD group,the neurons in GL group were arranged relatively neatly,the number of Nissl bodies was increased,the neurological deficit score,brain water content,neuronal apoptosis rate,TNF-α,IL-6,p-NF-κB/NF-κB protein expression were decreased,and Drd2 and Cryab protein expression were increased(P<0.05).Compared with GL group,the above indexes in haloperidol group were significantly reversed(P<0.05).Conclusion:GL can inhibit the inflammatory response and neuronal apoptosis in neonatal rats with HIBD,and reduce the nerve injury in neonatal rats with HIBD,The mechanism may be relate to the activation of Drd2/Cryab/NF-κB signaling pathway.