右美托咪定对丙泊酚诱导的发育期大鼠远期学习记忆障碍的影响及机制研究  

Effect of dexmedetomidine on propofol⁃induced remote learning memory impairment in developing rats and mechanism

作　　者：陈余 杨剑 Chen Yu;Yang Jian(College of Anesthesiology,Guizhou Medical University,Guiyang 550004,China;Department of Anesthesiology,Chongqing Dazu Tradi-tional Chinese Medicine Hospital,Chongqing 402360,China;Department of Anesthesiology,Affiliated Hospital of Guizhou Medical Uni-versity,Guiyang 550004,China)

机构地区：[1]贵州医科大学麻醉学院,贵阳550004 [2]重庆市大足区中医院麻醉科,重庆402360 [3]贵州医科大学附属医院麻醉科,贵阳550004

出　　处：《国际麻醉学与复苏杂志》2024年第9期911-916,共6页International Journal of Anesthesiology and Resuscitation

摘　　要：目的探讨右美托咪定(Dex)能否通过调控蛋白激酶A(PKA)改善丙泊酚诱导的发育期大鼠学习记忆障碍,以及对海马组织细胞焦亡的影响。方法选择7日龄SD大鼠120只,按照随机数字表法分为6组(每组20只):对照组(Con组)、丙泊酚组(Pro组)、Dex组、Dex预给药组(DP组)、PKA特异性拮抗剂(H89)+DP组(HDP组)、二甲基亚砜(DMSO)+DP组(CDP组)。Pro组腹腔注射丙泊酚50 mg/kg,待大鼠翻正反射恢复后(40~60 min)追加丙泊酚50 mg/kg;Con组腹腔注射等量生理盐水;Dex组腹腔注射Dex 25μg/kg;DP组腹腔注射Dex 25μg/kg,20 min后按照Pro组给药;HDP组和CDP组分别腹腔注射H890.05 mg/kg和0.1 ml DMSO,1 h后给药同DP组。大鼠分组处理后同窝饲养至30日龄,采用Morris水迷宫实验检测逃避潜伏期和穿越平台次数,采用免疫印迹法检测海马组织磷酸化蛋白激酶A(p‑PKA)、核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3(NLRP3)、胱天蛋白酶‑1(caspase‑1)、gasdermin‑D(GSDMD)蛋白水平,乳酸脱氢酶(LDH)试剂盒检测海马组织LDH浓度。结果与Con组比较:Pro组、DP组、HDP组及CDP组大鼠Morris水迷宫实验第2~4天逃避潜伏期延长,穿越平台次数减少(均P<0.05);海马组织p‑PKA蛋白水平降低,NLRP3、caspase‑1和GSDMD蛋白水平和LDH浓度升高(均P<0.05)。与Pro组比较:Dex组、DP组和CDP组大鼠第2~4天逃避潜伏期缩短,穿越平台次数增多(均P<0.05);海马组织p‑PKA蛋白水平升高,NLRP3、caspase‑1和GSDMD蛋白水平和LDH浓度降低(均P<0.05)。与DP组、CDP组比较:HDP组大鼠第2~4天逃避潜伏期延长,穿越平台次数减少(均P<0.05);海马组织p‑PKA蛋白水平降低,NLRP3、caspase‑1和GSDMD蛋白水平和LDH浓度升高(均P<0.05)。其余指标差异均无统计学意义(均P>0.05)。结论Dex能够改善丙泊酚诱导的发育期大鼠学习记忆障碍,其机制可能与激活PKA下调NLRP3/caspase‑1信号通路从而减轻海马组织细胞焦亡有�Objective To investigate whether dexmedetomidine(Dex)can modulate the effect of protein kinase A(PKA)on the improvement of propofol‑induced learning memory function and the effect on hippocampal pyroptosis in developing rats.Meth⁃ods According to the random number table method,1207‑day‑old SD rats were divided into six groups(n=20):a control(Con)group,a propofol(Pro)group,a Dex group,a Dex pre‑administration(DP)group,a PKA specific antagonist(H89)+DP(HDP)group,and a di‑methyl sulfoxide(DMSO)+DP(CDP)group.Rats in the Pro group were intraperitoneally injected with 50 mg/kg of propofol,followed by additional administration of 50 mg/kg propofol after the recovery of righting reflex(40-60 min).The Con group was intraperitoneally injected with an equal amount of normal saline.The Dex group was intraperitoneally injected with 25μg/kg of Dex.The DP group was intraperitoneally injected with 25μg/kg of Dex,followed by the same administration regimen with the Pro group 20 min later.Both the HDP group and the CDP group were intraperitoneally injected with 0.05 mg/kg of H89 and DMSO at 0.1 ml,respectively,followed by the same administration regimen with the DP group 1 h later.The rats were raised in the same litter until 30 d of age.Then,the Morris water maze was used to detect the prolonged escape latency and the number of platform crossings.The levels of hippocampal phosphorylated‑PKA(p‑PKA),nucleotide‑binding domain leucine‑rich repeat and pyrin domain containing receptor 3(NLRP3),cas‑pase‑1,and gasdermin‑D protein(GSDMD)protein were detected by Western blot,while the lactate dehydrogenase(LDH)kit was uti‑lized to detect hippocampal LDH concentrations.Results Compared with the Con group,the Pro,DP,HDP,and CDP groups showed prolonged escape latency,with a decreased number of platform crossings on days 2-4(all P<0.05);the levels of hippocampal p‑PKA protein decreased,while the levels of NLRP3,caspase‑1,and GSDMD protein and LDH concentrations increased(all P<0.05).Compared with the Pro group

关 键 词：右美托咪定 发育期 学习记忆功能 丙泊酚 蛋白激酶A 大鼠 

分 类 号：R614[医药卫生—麻醉学]