The protective effect of dexmedetomidine on sevoflurane-induced cognitive impairment based on the Wnt/β-catenin signaling pathway
YANG Yong
CHEN Renjun
GE Jianling
WANG Wei
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 quad-rant 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).Hippocam-pal 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 dexme-detomidine 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 activat-ing the Wnt/β-catenin signaling pathway,reducing inflammation,and enhancing neurotransmitter activity.
Keywords：dexmedetomidinesevofluranecognitive impairmentwingless-type MMTV integration site family proteinglycogen synthase kinase 3β
Publication Date：2024-08-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 2063-2068 )