Effect of dexmedetomidine on expression of NR1 subunit-containing NMDA receptors and GluR2 subunit-containing AMPA receptors during hypoxic injury to rat hippocampal neurons

Abstract

Objective To evaluate the effect of dexmedetomidine on the expression of NR1 subunit-containing NMDA receptors and GluR2 subunit-containing AMPA receptors during hypoxic injury to rat hippocampal neurons. Methods The hippocampal neurons were isolated from Wistar rats within 24 h after birth and divided into 3 groups (n=24 each) using a random number table: control group (group C), hypoxia group (group H) and dexmedetomidine group (group D). The cells were subjected to hypoxia for 6 h to establish the model of neuronal hypoxic injury in H and D groups.In group D, 0.1 μmol/L dexmedetomidine was added at 6 h of hypoxia and neurons were incubated for 3 h, and then the culture medium was replaced with a normal medium and neurons were incubated for 24 h. The neuronal viability was measured by CCK-8 assay, the leakage of LDH was detected, and the leakage rate was calculated.The expression of NR1 subunits-containing NMDA receptors and GluR2 subunits-containing AMPA receptors was detected by Western blot.The concentration of calcium ion in cytoplasm was measured using Fluo-3AM. Results Compared with group C, the neuronal viability was significantly decreased, the LDH leakage rate was increased, the expression of NR1 subunits-containing NMDA receptors in the membrane was up-regulated, the expression of GluR2 subunits-containing AMPA receptors was down-regulated, and the concentration of calcium ion in cytoplasm was increased in H and D groups (P<0.05). Compared with group H, the neuronal viability was significantly increased, the LDH leakage rate was decreased, the expression of NR1 subunits-containing NMDA receptors in the membrane was down-regulated, the expression of GluR2 subunits-containing AMPA receptors was up-regulated, and the concentration of calcium ion in cytoplasm was decreased in group D (P<0.05). Conclusion The mechanism by which dexmedetomidine reduces hypoxic injury to rat hippocampal neurons may be related to inhibiting up-regulation of the expression of NR1 subunits-containing NMDA receptors in the membrane and down-regulation of the expression of GluR2 subunits-containing AMPA receptors. Key words: Dexmedetomidine; Anoxia; Neurons; Receptors, N-methyl-D-aspartate; Receptors, AMPA