关键词: 低氧预适应, 脑中动脉阻塞, 凋亡, BCL-xL, p38 MAPK

Abstract: Objective To explore the role of P38 mitogen actived protein kinase (P38MAPK)-BCL-xL antiapoptotic pathway in hypoxic preconditioning (HPC)-induced neuroprotection in ischemic brain. Methods SPF grade male BALB/c mice (18~22g, 8~10w) were randomly divided into four groups: normoxic sham (NS), normoxic ischemia (NI), HPC sham (HS) and HPC-ischemia (HI) groups. Using HPC, middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia mouse models and P38MAPK inhibitor SB203580 injection, the changes in neural apoptosis were observed by TUNEL staining, the expression of antiapoptotic protein BCL-xL was detected by Western blot. The interaction between BCL-xL and P38MAPK was determined by immunoprecipitation technique. Results HPC could inhibit neural apoptosis and elevated BCL-xL protein level in mitochondria significantly in the penumbra of ischemic cortex. Intracerebroventricular injection of P38MAPK inhibitor SB203580 abolished the HPC-induced neuroprotection. Furthermore, the result of immunoprecipitation showed that there was an interaction between BCL-xL and P38MAPK. Conclusion HPC could protect the brain against MCAO-induced ischemic injuries via P38MAPK-BCL-xL antiapoptotic pathway in mice.

Key words: HPC, MCAO, Apoptosis, BCL-xL, p38 MAPK