基底外侧杏仁核-上边缘皮质BDNF在小鼠围术期神经认知紊乱中的作用:与TrkB受体的关系  

Role of BDNF in basolateral amygdala-prelimbic cortex in perioperative neurocognitive disorders and relationship with TrkB receptors in mice

作　　者：宋雨桐 仲达 高银 孙晓玉 高灿 Song Yutong;Zhong Da;Gao Yin;Sun Xiaoyu;Gao Can(Jiangsu Province Key Laboratory of Anesthesiology&Jiangsu Province Key Laboratory of Anesthetic and Analgesia Application Technology Xuzhou Medical University,Xuzhou 221004,China;Department of Anesthesiology,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China)

机构地区：[1]徐州医科大学,江苏省麻醉学重点实验室,江苏省麻醉与镇痛应用技术重点实验室,221004 [2]上海交通大学医学院附属仁济医院麻醉科,200127

出　　处：《中华麻醉学杂志》2021年第6期674-679,共6页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81870852);江苏省自然科学基金(BK20181146);江苏省高校自然科学基金(18KJA320007);江苏省研究生创新课题(KYCX19-2226);江苏省大学生创新创业训练计划(201910313002Z)。

摘　　要：目的:评价基底外侧杏仁核(BLA)-上边缘皮质(PL)脑源性神经营养因子(BDNF)在小鼠围术期神经认知紊乱中的作用及其与酪氨酸激酶受体B(TrkB)受体的关系。方法:清洁级健康C57BL/6J小鼠48只,6月龄,体重25~30 g,采用随机数字表法分为4组(n=12):对照组(C组)、手术组(S组)、BLA区BDNF过表达组(B组)和BLA区BDNF过表达+PL区注射ANA-12组(A组)。S组于条件恐惧记忆实验训练期结束后30 min时行腹部探查术;B组在BLA区注射重组腺病毒0.3μl,3周后进行条件恐惧记忆实验,于训练期结束后30 min时行腹部探查术;A组在BLA区域注射重组腺病毒0.3μl,并在PL区置管,3周后进行条件恐惧记忆实验,于训练期开始前30 min时,经PL套管注射TrkB受体拮抗剂ANA-120.25μg,于训练期结束后30 min行腹部探查术。均于条件恐惧记忆实验训练期结束后24 h开始测试期,计算僵直时间百分比。行为学测试结束后30 min,采用免疫印迹法检测脑区BDNF、磷酸化TrkB(p-TrkB)和磷酸化细胞外调节蛋白激酶(p-ERK1/2)的表达,采用反转录荧光定量PCR法进行检测BLA区BDNF mRNA的表达。结果:与C组比较,S组环境和声音依赖的僵直时间百分比降低,BLA区BNDF及其mRNA、PL区BDNF、p-TrkB、p-ERK1/2表达下调(P<0.05)。与S组比较,B组环境和声音依赖的僵直时间百分比升高,BLA区BNDF及其mRNA表达上调,PL区BDNF、p-TrkB、p-ERK1/2表达上调(P<0.05);与B组比较,A组环境和声音依赖的僵直时间百分比降低,PL区p-TrkB和p-ERK1/2表达下调(P<0.05)。结论:小鼠围术期神经认知紊乱的发生机制可能与BLA区BDNF表达下调导致BLA区向PL区释放的BDNF减少,降低突触后TrkB受体磷酸化水平有关。Objective To evaluate the role of basolateral amygdala(BLA)-prelimbic cortex(PL)brain-derived neurotrophic factor(BDNF)in perioperative neurocognitive disorders(PND)and its relationship with tyrosine kinase B(TrkB)receptors in mice.Methods Forty-eight clean-grade healthy C57BL/6J mice,aged 6 months,weighing 25-30 g,were divided into 4 groups(n=12 each)using a random number table method:control group(group C),surgery group(group S),BDNF overexpression in BLA group(group B)and BDNF overexpression in BLA+ANA-12 injection in PL group(group A).In group S,at 30 min after the end of training session of fear conditioning system,exploratory laparotomy was performed.In group B,recombinant adenovirus 0.3μl was injected in BLA,fear conditioning test was performed 3 weeks later,and exploratory laparotomy was performed at 30 min after the end of the training session of fear conditioning system.In group A,recombinant adenovirus 0.3μl was injected in BLA,catheterization was performed in PL,the fear conditioning test used performed 3 weeks later,TrkB receptor antagonist ANA-120.25μg was given in PL starting from 30 min before training session,and exploratory laparotomy was performed at 30 min after training session.Test session was started at 24 h after the end of training session of fear conditioning system,and the percentage of time spent freezing was calculated in all groups.At 30 min after the end of the behavioral test,the expression of BDNF in brain areas,phosphorylated TrkB(p-TrkB)and phosphorylated extracellular signal-regulated kinase 1/2(p-ERKl/2)was determined by Western blot,and the expression BDNF mRNA in BLA was detected using reverse transcription fluorescence quantitative polymerase chain reaction assay.Results Compared with group C,the percentage of time spent freezing was significantly decreased,and expression of BNDF protein and its mRNA in BLA and BDNF,p-TrkB and p-ERK1/2 in PL was down-regulated in group S(P<0.05).Compared with group S,the percentage of time spent freezing was significantly increased,and e

关 键 词：杏仁核 额叶前皮质 脑源性神经营养因子 认知障碍 

分 类 号：R749.1[医药卫生—神经病学与精神病学]