Abstract: Objective To investigate the effects of dexmedetomidine(Dex) on learning, memory ability and GluR2[the subunit that restricts Ca2+ permeability of a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors] protein expression in hippocampal CA1 neurons of rats subjected to global ischemia/reperfusion(I/R). Methods Forty-eight male SD rats were randomly divided into four groups(n=12): group sham operation (groupS), group global I/R (group I/R), global I/R+Dex 100 μg/kg (groupD), yohimbine 0.1 mg/kg+Dex 100 μg/kg+global I/R (group YD). The model of global ischemia was established with method of 4-vessel occlusion with five minutes followed by reperfusion. Yohimbine and/or Dex was administered intraperitoneally 30 min before ischemia. While eaqual volume of normal saline was injected intraperitoneally in group S and I/R respectively. Spatial learning and memory function of rats in each group was tested by Morris water maze after seven days of reperfusion. To examine GluR2 protein abundance, Western blot analysis was performed on samples isolated from hippocampal CA1 subfield from each group at 72 h after reperfusion. Results Compared with group S, the escape latency in group I/R was significantly longer(P<0.05), and the time in the target quadrant of the platform[(32.1±5.0) s vs (48.7±5.5) s] and times across the platform[(1.5±0.8) vs(5.0±1.2) ] in group I/R were significantly decreased(P<0.05). Compared with group I/R, the escape latency in group D was significantly decreased(P<0.05), and the time in the target quadrant of the platform [(40.6±2.1) s vs (32.1±5.0) s] and times across the platform[(3.3±0.5) vs(1.5±0.8)] in group D were significantly increased(P<0.05). Compared with group D, the escape latency in group YD was significantly increased(P<0.05), and the time in the target quadrant of the platform[(32.2±6.0) s vs (40.6±2.1) s] and times across the platform[(1.6±0.8) vs (3.3±0.5)] in group YD were significantly decreased(P<0.05), there was no significant difference between group I/R and group YD(P>0.05), the abundance of GluR2 protein from hippocampal CA1 subfield from group I/R at 72 h after reperfusion was significantly downregulated(P<0.01), the downregulation of GluR2 protein in group I/R was inhibited in group D at 72 h after reperfusion(P<0.05), and the effect was abolished ingroup YD(P<0.05), there was no significant difference between group I/R and group YD(P>0.05). Conclusions Dex can improve learning and memory ability of rats subjected to cerebral I/R, and the inhibition of downregulation of GluR2 in hippocampal CA1 neurons of rats following global ischemia may be involved in the mechanism.
|