Effect of p38 MAPK pathway on isoflurane-induced neuronal apoptosis in hippocampus of neonatal rats / 中国药理学通报

ABSTRACT

Aim To investigate the effect of isoflurane on the phosphorylation of p38 mitogen-activated protein kinase (MAPK)in the hippocampus of neonatal rats, and the effect of p38 MAPK pathway on isoflurane-in-duced neuronal apoptosis.Methods Forty-eight neo-natal rats on postnatal day 7 were assigned randomly into four groupsDMSO group (group Air +DMSO), p38 MAPK inhibitor SB203580 group (group Air +SB20 ),isoflurane +DMSO group (group Iso +DM-SO),and isoflurane +SB203580 group (group Iso +SB20 ).Rats were exposed to air or isoflurane (volume fraction of 0.01 1 )for 4h.The p38 inhibitor SB203580 (20 nmol)or DMSO (volume fraction of 0.1 )5μl was intraventricularly administered 30 min before the expo-sure.The brains of some rats in each group were per-fused and embedded by paraffin 6h after the exposure. Neuronal apoptosis in the hippocampal CA1 area was detected by terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL)(n =6). The hippocampal tissues of the other rats in each group were dissected 6h after the exposure,and the protein expressions of phospho-p38 (p-p38 ),p38,cleaved caspase-3,phospho-NF-κB (p-NF-κB ),Bcl-2 and Bax were detected by Westem blot (n =6).Results The number of TUNEL positive cells in the hippocam-pal CA1 region in group Iso +DMSO increased by 4.8 fold compared with that in group Air +DMSO (P <0.01 ),while the number of TUNEL positive cells in group Iso +SB20 decreased by 3 /5 compared with that in group Iso +DMSO (P <0.01 ).The protein expres-sion of cleaved caspase-3 in group Iso +DMSO signifi-cantly increasd (P =0.003)compared to that in group Air +DMSO,which was significantly decreasd in group Iso +SB20 (P =0.007 ).In addition,isoflurane also increased the protein expression of p-p38,p-NF-κB and Bax,decreased the level of Bcl-2,and reduced the ratio of Bcl-2 /Bax compared with control animals (P <0.01 ,P =0.004,P <0.01 ,P <0.01 ,P <0.01 ,respectively).Howerver,SB203580 partly at-tenuated the isoflurane-induced protein change above. Conclusion Isoflurane induces neuroapoptosis in neo-natal rat hippocampus by the activation of p38 MAPK pathway.