Abstract:

Objective To study the protective effect and possible mechanism of dexmedetomidine on sevoflurane-induced cognitive impairment. Methods 40 rats were randomly divided into a blank group， model group， dexmedetomidine group， and combination group， 10 for each group. A rat model of sevoflurane-induced cognitive impairment was established in the model group， dexmedetomidine group， and combination group. The dexmedetomidine group and combination group were intraperitoneally injected with dexmedetomidine of 50 μg/kg 30 min before modeling， so was the combination group injected with sulindac of 5 mg/kg. The blank group and model group were intravenously injected with equal amount of saline. Morris water maze test was used to detect cognitive function. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of homocysteine （Hcy） and monocyte chemoattractant protein-1 （MCP-1）； high-performance liquid chromatography was used to detect hippocampal glutamate （Glu） and γ-aminobutyric acid （GABA） contents. Immunoblotting was used to detect hippocampal glycogen synthase kinase 3β （GSK-3β） and β-catenin protein expression levels. Results The escape latency in the dexmedetomidine group rats was shorter than that in the model group （P < 0.05）， the number of crossing the original platform was greater than that in the model group （P < 0.05）， and duration staying in the original platform quadrant was longer than that in the model group （P < 0.05）. The escape latency in the combination group was longer than that in the dexmedetomidine group （P < 0.05）， the number of crossing the original platform was smaller than that in the dexmedetomidine group （P < 0.05）， and duration staying in the original platform quadrant was shorter than that in the dexmedetomidine group （P < 0.05）. Serum levels of Hcy and MCP-1 were higher in the model group than in the blank group （P < 0.05）， lower in the dexmedetomidine group than in the model group （P < 0.05）， and higher in the combination group than in the dexmedetomidine group （P < 0.05）. Hippocampal Glu content was higher in the model group than in the blank group （P < 0.05）， while GABA content was lower （P < 0.05）. Hippocampal Glu content was lower in the dexmedetomidine group than in the model group （P < 0.05）， whereas GABA content was higher group （P < 0.05）. Hippocampal Glu content was higher in the combination group than in the dexmedetomidine group （P < 0.05）， and GABA content was lower （P < 0.05）. Hippocampal GSK-3β protein expression level was higher in the model group than in the blank group （P < 0.05）， but the β-catenin protein expression level was lower （P < 0.05）. Hippocampal GSK-3β protein expression level was lower in the dexmedetomidine group than in the model group （P < 0.05）， while β-catenin protein expression level was higher （P < 0.05）. Hippocampal GSK-3β protein expression level was higher in the combination group than in the dexmedetomidine group （P < 0.05）， whereas β-catenin protein expression level was lower （P < 0.05）. Conclusions Dexmedetomidine may improve cognitive function in rats with sevoflurane-induced cognitive impairment by activating the Wnt/β-catenin signaling pathway， reducing inflammation， and enhancing neurotransmitter activity.

Key words: dexmedetomidine, sevoflurane, cognitive impairment, wingless-type MMTV integration site family protein, glycogen synthase kinase 3β