基于Wnt/β-catenin信号通路研究右美托咪定对七氟烷诱发认知功能损伤的保护作用

The protective effect of dexmedetomidine on sevofluraneinduced cognitive impairment based on the Wnt/βcatenin signaling pathway

目的研究右美托咪定对七氟烷诱发认知功能损伤的保护作用及可能机制。方法40只大鼠随机分为空白组、模型组、右美托咪定组及联合组,每组各10只。模型组、右美托咪定组、联合组建立七氟烷认知损伤模型。右美托咪定组、联合组大鼠建模前30 min腹腔注射右美托咪定50μg/kg,联合组另腹腔注射舒林酸5 mg/kg,空白组、模型组静脉注射等量生理盐水。Morris水迷宫测试检测认知功能;酶联免疫吸附实验(ELISA)检测血清同型半胱氨酸(Hcy)、单核细胞趋化蛋白-1(MCP-1)水平;高效液相色谱仪检测海马组织谷氨酸(Glu)、γ-氨基丁酸(GABA)含量;免疫印迹法检测海马组织糖原合成酶激酶3β(GSK-3β)、β-连环蛋白(β-catenin)蛋白表达量。结果右美托咪定组大鼠逃避潜伏期短于模型组(P<0.05),穿越原平台次数多于模型组(P<0.05),原平台象限停留时间长于模型组(P<0.05);联合组大鼠逃避潜伏期长于右美托咪定组(P<0.05),穿越原平台次数少于右美托咪定组(P<0.05),原平台象限停留时间短于右美托咪定组(P<0.05)。模型组大鼠血清Hcy、MCP-1水平高于空白组(P<0.05),右美托咪定组低于模型组(P<0.05),联合组高于右美托咪定组(P<0.05)。模型组海马组织GLu含量高于空白组(P<0.05),GABA含量低于空白组(P<0.05);右美托咪定组海马组织GLu含量低于模型组(P<0.05),GABA含量高于模型组(P<0.05);联合组海马组织GLu含量高于右美托咪定组(P<0.05),GABA含量低于右美托咪定组(P<0.05)。模型组海马组织GSK-3β蛋白表达量高于空白组(P<0.05),β-catenin蛋白表达量低于空白组(P<0.05);右美托咪定组海马组织GSK-3β蛋白表达量低于模型组(P<0.05),β-catenin蛋白表达量高于模型组(P<0.05);联合组海马组织GSK-3β蛋白表达量高于右美托咪定组(P<0.05),β-catenin蛋白表达量低于右美托咪定组(P<0.05)。结论右美托咪定可能通过激活Wnt/β-catenin信号通路改善七氟烷诱发认知功能损伤大鼠的认知功能,减轻炎症反应,增强神经递质活性。

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 50μg/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)andγ-aminobutyric acid(GABA)contents.Immunoblotting was used to detect hippocampal glycogen synthase kinase 3β(GSK-3β)andβ-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-3βprotein expression level was higher in the model group than in the blank group(P<0.05),but theβ-catenin protein expression level was lower(P<0.05).Hippocampal GSK-3βprotein expression level was lower in the dexmedetomidine group than in the model group(P<0.05),whileβ-catenin protein expression level was higher(P<0.05).Hippocampal GSK-3βprotein expression level was higher in the combination group than in the dexmedetomidine group(P<0.05),whereasβ-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.