摘要
目的探讨右美托咪定对咪达唑仑麻醉所致认知功能障碍的保护作用及其机制。方法将120只无特定病原体级雄性SD大鼠按照随机数字法分为正常对照组、咪达唑仑组、右美托咪定50μg/kg组、右美托咪定75μg/kg组,每组30只,每组大鼠随机分为2个亚组(各15只),分别进行Morris水迷宫实验与蛋白含量检测。正常对照组大鼠不予任何药物处理,咪达唑仑组大鼠建立咪达唑仑麻醉模型,右美托咪定50μg/kg和75μg/kg组建立咪达唑仑联合右美托咪定麻醉模型,其中一个亚组分别于麻醉第1、3、5、7天待大鼠麻醉清醒后行定位航行实验测定大鼠学习能力,麻醉第7天行空间探索实验测定记忆能力;另一个亚组分别于麻醉第3、5、7天检测磷酸化胞外信号调节激酶1/2(p-ERK1/2)、磷酸化cAMP反应元件结合蛋白(p-CREB)水平。结果逃避潜伏期组间和时点间的主效应差异有统计学意义(P<0.01),组间和时点间存在交互作用(P<0.01),麻醉第3、5、7天各组大鼠逃避潜伏期呈下降趋势,咪达唑仑组、右美托咪定50 mg/kg组、右美托咪定75 mg/kg组各时点间逃避潜伏期均长于正常对照组,右美托咪定50 mg/kg组和右美托咪定75 mg/kg组均短于咪达唑仑组,右美托咪定75 mg/kg组短于右美托咪定50 mg/kg组(P<0.05)。麻醉第7天穿越平台位置次数及停留在第三象限时间比率对比,正常对照组>右美托咪定75 kg/mg组>右美托咪定50 kg/mg组>咪达唑仑组,组间两两比较差异均有统计学意义(P<0.05);麻醉第3、5、7天,咪达唑仑组、右美托咪定50 mg/kg组、右美托咪定75 mg/kg组的p-ERK1/2和p-CREB蛋白水平低于正常对照组,右美托咪定50 mg/kg组和右美托咪定75 mg/kg高于咪达唑仑组,右美托咪定75 mg/kg组高于右美托咪定50 mg/kg组(P<0.05)。结论右美托咪定能够改善咪达唑仑麻醉所致大鼠认知功能损害症状,通过调节p-ERK1/2及p-CREB等的表达发挥保护大鼠认知功能的作用。
Objective To investigate the protective effect and mechanism of dexmedetomidine on cognitive impairment caused by midazolam anesthesia.Methods 120 free male SD rats with no specific pathogen were divided into a normal control group,a midazolam group,a dexmedetomidine 50μg/kg group,and a dexmedetomidine 75μg/kg group according to the random number method,with 30 rats in each group,which were randomly divided into 2 subgroups(15 rats each),and the Morris water maze test and protein content detection were performed respectively.The rats in the normal control group were not treated with any drugs,the rats in the midazolam group were established as a midazolam anesthesia model,and the rats in the dexmedetomidine 50μg/kg and 75μg/kg groups were established as midazolam and dexmedetomidine combination model.Each one of the subgroups was performed a positioning navigation experiment to determine the learning ability of rats after anesthesia and awake on the 1st,3rd,5th and 7th days of anesthesia,and a space exploration experiment to determine memory ability on the 7th day of anesthesia.In each one of the other subgroups,the levels of phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2)and phosphorylated cAMP response element binding protein(p-CREB)were detected on the 3rd,5th and 7th days of anesthesia.Results There were significant differences in the main effects of escape latency between groups and time points(P<0.01),and there was an interaction between groups and time points(P<0.01).The escape latency of the rats in each group showed a downward trend on the 3rd,5th and 7th day of anesthesia.The escape latency of the midazolam group,dexmedetomidine 50 mg/kg group,and dexmedetomidine 75 mg/kg group was longer than the normal control group,dexmedetomidine 50 mg/kg group and dexmedetomidine 75 mg/kg group shorter than the midazolam group,dexmedetomidine 75 mg/kg group shorter than the dexmedetomidine 50 mg/kg group(P<0.05).Comparison of the number of times of crossing the platform position on the 7th day of anesthesia and the ratio of staying in the third quadrant:the normal control group>dexmedetomidine 75 kg/mg group>dexmedetomidine 50 kg/mg group>midazolam group,the differences between every two groups were statistically significant(P<0.05).On the 3rd,5th and 7th day of anesthesia,the protein levels of p-ERK1/2 and p-CREB in the midazolam group,dexmedetomidine 50 mg/kg group,and dexmedetomidine 75 mg/kg group were lower than those of the normal control group,dexmedetomidine 50 mg/kg group and dexmedetomidine 75 mg/kg group higher than the midazolam group,dexmedetomidine 75 mg/kg group was higher than the dexmedetomidine 50 mg/kg group(P<0.05).Conclusion Dexmedetomidine can improve the symptoms of cognitive impairment induced by midazolam anesthesia in rats,and protect the cognitive function of rats by regulating the expressions of p-ERK1/2 and p-CREB.
作者
董浩垚
侯俊德
迟晓慧
王晓微
赵广平
陈永学
DONG Haoyao;HOU Junde;CHI Xiaohui;WANG Xiaowei;ZHAO Guangping;CHEN Yongxue(School of Clinical Medicine,Hebei Engineering University,Handan 056008,China;Department of Anesthesiology,Handan Central Hospital,Handan 056008,China)
出处
《医学综述》
CAS
2021年第12期2473-2477,共5页
Medical Recapitulate
基金
河北省重点研发计划自筹项目(182777222)。
关键词
认知功能障碍
右美托咪定
咪达唑仑
麻醉
学习能力
记忆能力
Cognitive dysfunction
Dexmedetomidine
Midazolam
Anesthesia
Learning ability
Memory ability
