中央杏仁核多巴胺受体在丙泊酚降低PTSD小鼠焦虑水平中的作用  

Role of dopamine receptors in central amygdala in reduction of anxiety level by propofol in a mouse model of post-traumatic stress disorder

作　　者：隋晓凯 陈婷[1] 孙嘉慧 张学敏 陶万江 宋辉琼 王杰 张宗泽[1] 陈畅[1] Sui Xiaokai;Chen Ting;Sun Jiahui;Zhang Xuemin;Tao Wanjiang;Song Huiqiong;Wang Jie;Zhang Zongze;Chen Chang(Department of Anesthesiology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China;Department of Anesthesiology,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China;Department of Anesthesiology,Wuhan Fourth Hospital,Wuhan 430033,China;Wuhan Institute of Physics and Mathematics,Innovation Academy for Precision Measurement Science and Technology,Wuhan 430071,China)

机构地区：[1]武汉大学中南医院麻醉科,武汉430071 [2]首都医科大学附属北京朝阳医院麻醉科,北京100027 [3]武汉市第四医院麻醉科,武汉430033 [4]武汉物理与数学研究所精密测量科学与技术创新研究院,武汉430071

出　　处：《中华麻醉学杂志》2024年第11期1333-1338,共6页Chinese Journal of Anesthesiology

基　　金：中央高校基本科研专项资金(2042024YXA005);国家自然科学基金(82371290);湖北省中央引导地方科技发展专项(2022BGE236)。

摘　　要：目的探讨中央杏仁核(CeA)多巴胺受体(DRD)在丙泊酚降低创伤后应激障碍(PTSD)小鼠焦虑水平中的作用。方法SPF级健康成年雄性C57BL/6小鼠56只,10周龄,体质量20~25 g,采用随机数字表法分为7组(n=8):对照组(C组)、PTSD组(P组)、PTSD+丙泊酚组(PP组)、PTSD+脂肪乳剂组(PF组)、PTSD+丙泊酚+生理盐水组(PPN组)、PTSD+丙泊酚+DRD1阻断剂组(PP+DRD1-Ant组)和PTSD+丙泊酚+DRD2阻断剂组(PP+DRD2-Ant组)。采用连续3 d足底电击的方法制备PTSD小鼠模型,PP组小鼠在模型制备成功后腹腔注射丙泊酚120 mg/kg,PF组小鼠腹腔注射等体积脂肪乳剂。PPN组、PPDRD1-Ant组和PPDRD2-Ant组小鼠在双侧CeA脑区分别套管注射等体积生理盐水、DRD1阻断剂hydrochloride和DRD2阻断剂Eticlopride hydrochloride,30 min后待阻断剂药效达峰,腹腔注射丙泊酚120 mg/kg。于注射丙泊酚后4 h(T_(1))和第3天(T_(2))时采用旷场实验和高架十字迷宫实验检测小鼠焦虑水平。结果与C组相比,P组小鼠T_(1)和T_(2)时开放臂和中央区停留时间和进入次数减少(P<0.001);与P组相比,PP组小鼠T_(1)时开放臂和中央区停留时间和进入次数增加(P<0.001),T_(2)时差异无统计学意义,PF组小鼠T_(1,2)时上述指标差异无统计学意义(P>0.05);与PPN组相比,PP+DRD2-Ant组小鼠T_(1)时开放臂和中央区停留时间和进入次数减少(P<0.001),PP+DRD1-Ant组小鼠T_(1)时差异无统计学意义(P>0.05)。结论DRD2激活参与了丙泊酚降低PTSD小鼠焦虑水平的过程。Objective To investigate the role of dopamine receptors in the central amygdala(CeA)in reduction of the anxiety level by propofol in a mouse model of post-traumatic stress disorder(PTSD).Methods Fifty-six SPF healthy adult male C57BL/6 mice,aged 10 weeks,weighing 20-25 g,were divided into 7 groups(n=8 each)using a random number table method:control group(C group),PTSD group(P group),PTSD+propofol group(PP group),PTSD+fat emulsion group(PF group),PTSD+propofol+normal saline group(PPN group),PTSD+propofol+dopamine receptor D1(DRD1)antagonist group(PP+DRD1-Ant group),and PTSD+propofol+DRD2 antagonist group(PP+DRD2-Ant group).The PTSD model was developed by continuous plantar electric shock for 3 days.Propofol 120 mg/kg was intraperitoneally injected after successful establishment of the model in PP group,and the equal volume of fat emulsion was intraperitoneally injected in PF group.In PPN group,PP+DRD1-Ant group and PP+DRD2-Ant group,the equal volume of normal saline,DRD1 antagonist hydrochloride and DRD2 antagonist eticlopride hydrochloride were injected in bilateral CeA regions,respectively,30 min later the efficacy of drugs reached the peak,and then propofol 120 mg/kg was intraperitoneally injected.The anxiety levels were measured at 4 h(T_(1))and day 3 after propofol injection(T_(2))by the open field test and elevated cross maze test.Results Compared with C group,the time spent entering the open and central areas was significantly shortened at T_(1),2,and the number of entering the open and central areas was decreased at T_(1),2 in P group(P<0.001).Compared with P group,the time spent entering the open and central areas was significantly prolonged at T_(1),the number of entering the open and central areas was increased at T_(1)(P<0.001),and no significant change was found at T_(2) in PP group(P>0.05),and no significant change was found in the aforementioned parameters at T_(1,2) in PF group(P>0.05).Compared with PPN group,the time spent entering the open and central areas was significantly shortened at T_(1),an

关 键 词：中央杏仁核 受体 多巴胺 二异丙酚 应激障碍 创伤性 焦虑 

分 类 号：R614[医药卫生—麻醉学]