Effect of propofol postconditioning on activities of pro-apoptotic proteins in rat cortical neurons subjected to OGD/R: the relationship with p38MAPK signaling pathway / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of propofol postconditioning on the activities of proapoptotic proteins Bid,Bim and Puma in rat cortical neurons subjected to oxygen-glucose deprivation/restoration (OGD/R) and the relationship with p38 mitogen-activated protein kinase (p38MAPK) signaling pathway.Methods The cortical neurons obtained from Sprague-Dawley rats (＜24 h after birth) were cultured in vitro and seeded in 6-well culture palate (2 ml/well).The cortical neurons were randomly divided into 4 groups (n =42 each) using a random number tablecontrol group (group C),OGD/R group,propofol postconditioning group (group P),and propofol postconditioning + p38MAPK inhibitor SB202190 group (group PS).The neurons were subjected to O2-glucose deprivation for 90 min followed by restoration of O2-glucose supply for 24 h.In P and PS groups,propofol with the final concentration of 50 μmol/L was added to the culture medium immediately after restoration of O2-glucose supply,and the neurons were cultured for 2 h.SB202190 with the final concentration of 50 μmol/L was added to the culture medium at 1 h before O2-glucose deprivation,and the neurons were cultured for 2 h.The neuronal apoptosis was detected using Annexin V-FITC/PI double staining combined with flow cytometry,the number of viable neurons was evaluated by methyl thiazolyl tetrazolium assay,and the amount of lactic dehydrogenase (LDH) released was measured using colorimetric method.Mitochondrial membrane potential (MMP) was assessed by JC-1 fluorescence assay.The expression of Bid,Bim and Puma proteins was determined by Western blot.Results Compared with group C,the apoptosis rate and amount of LDH released were significantly increased,the neuronal survival rate and MMP were significantly decreased,and the expression of Bid,Bim and Puma was significantly up-regulated in group OGD/R (P＜0.05).Compared with group OGD/R,the apoptosis rate and amount of LDH released were significantly decreased,the neuronal survival rate and MMP were significantly increased,and the expression of Bid,Bim and Puma was significantly down-regulated in P and PS groups (P＜0.05).Compared with group P,the apoptosis rate and amount of LDH released were significantly increased,the neuronal survival rate and MMP were significantly decreased,and the expression of Bid,Bim and Puma was significantly up-regulated in group PS (P＜0.05).Conclusion Propofol postconditioning reduces OGD/R-induced injury to rat cortical neurons through activating p38MAPK signaling pathway and inhibiting activities of pro-apoptotic proteins Bid,Bim and Puma.