Effect of dexmedetomidine on Src-mediated NR2A tyrosine phosphorylation in hippocampal neurons subjected to hypoxia-reoxygenation in mice / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of dexmedetomidine on Src-mediated NR2A tyrosine phosphorylation in hippocampal neurons subjected to hypoxia-reoxygenation (H/R) in mice.Methods C57 mice at 18 days of gestation were sacrificed by pulling neck,fetal mice were obtained by caesarean section,and hippocampal neurons were isolated.Neurons were cultured in culture medium for 7 days and then divided into 3 groups (n =30 each) using a random number table method:control group (group C),H/R group and dexmedetomidine group (D group).Hippocampal neurons were exposed to 95％ N2-5％ CO2 in an incubator at 37 ℃ for 4 h followed by reoxygenation with 95％ O2-5％ CO2 for 24 h to establish the model of H/R.Dexmedetomidine was given at a final concentration of 1 μ mol/L,and neurons were incubated for 4 h before establishing the model.The viability of hippocampal neurons was measured by MTT assay,TUNEL staining was used to observe apoptosis in hippocampal neurons,and the expression of c-Src,phosphorylated Src Y416 (p-Src Y416),NR2A,phosphorylated NR2A Y1325 (p-NR2A Y1325) and cleaved caspase-3.was determined by Western blot.Apoptosis index was calculated.Results Compared with group C,the viability of hippocampal neurons was significantly decreased,apoptosis index was increased,and the expression of p-Src Y416,p-NR2A Y1325 and cleaved caspase-3 was up-regulated in group H/R (P＜0.05).Compared with group H/R,the viability of hippocampal neurons was significantly increased,apoptosis index was decreased,and the expression of p-Src Y416,p-NR2A Y1325 and cleaved caspase-3 was down-regulated in group D (P＜0.05).There was no significant difference in the expression of c-Src and NR2A among three groups (P＞0.05).Conclusion Dexmedetomidine can inhibit apoptosis in hippocampal neurons subjected to H/R,and the mechanism may be associated with decreasing Src-mediated NR2A tyrosine phosphorylation in mice.