p38 MAPK-BCL-xL pathway was involved in HPC-induced neuroprotection in ischemic brain of mice

【摘要】：正Objective:To explore the role of p38 mitogen actived protein kinase(p38 MAPK)-BCL-xL antiapoptotic pathway in hypoxic preconditioning(HPC)-induced neuroprotection in ischemic brain.Methods:Male BALB/c mice(18-22 g,8-10 weeks) were randomly divided into four groups:H0 sham(H0+S),normoxic ischemia(H0+I), HPC sham(H4+S) and HPC-ischemia(H4+I) groups.Using HPC and middle cerebral artery occlusion(MCAO)- induced focal cerebral ischemia mouse models,and combined with TUNEL staining and Western blot techniques, changes in neural apoptosis in the penumbra of ischemic cortex,antiapoptotic protein BCL-xL distribution in cytosol or mitochondria and the affection of p38 MAPK inhibitor SB203580 were observed.In addition,the interaction between BCL-xL and p38 MAPK was determined by using immunoprecipitation technique.Results:HPC could inhibit neural apoptosis and elevated BCL-xL protein level in mitochondria significantly(P0.05,n=6 per group) in the penumbra of ischemic cortex.Intracerebroventricular injection of p38 MAPK inhibitor SB203580 abolished the HPC-induced neuroprotection.Furthermore,the result of immunoprecipitation showed that there was an interaction between BCL-xL and p38 MAPK.Conclusion:HPC could protect the brain against MCAO-induced ischemic injuries via d38 MAPK-BCL-xL antiapoptotic pathway in mice.