经皮耳穴迷走神经刺激对条件恐惧小鼠恐惧记忆及脾脏炎症反应的影响  

The effect of transcutaneous auricular vagus nerve stimulation on fear memory and spleen inflammatory response in fear‑conditioned mice

作　　者：杜英杰 白亚璠 张悦 刘敏[1] 张丛雅 陈一萌 陈红芽 李赫 王古岩 Du Yingjie;Bai Yafan;Zhang Yue;Liu Min;Zhang Congya;Chen Yimeng;Chen Hongya;Li He;Wang Guyan(Department of Anesthesiology,Beijing Tongren Hospital,Capital Medical University,Beijing 100730,China)

机构地区：[1]首都医科大学附属北京同仁医院麻醉科,北京100730

出　　处：《中华医学杂志》2025年第10期767-772,共6页National Medical Journal of China

基　　金：首都医科大学附属北京同仁医院青年拔尖人才(2023‑YJJ‑ZZL‑018);首都卫生发展科研专项(CFH2024‑2‑2058);国家自然科学基金(82270411);北京市医院管理局“登峰”计划(DFL20220203);首都医科大学科研培育项目(PYZ24106)。

摘　　要：目的观察经皮耳穴迷走神经刺激(taVNS)对条件恐惧小鼠恐惧记忆的影响,及其对脾脏炎症反应的调节作用。方法选取24只12周龄健康雄性C57BL/6J小鼠,采用随机数字表法分为taVNS组(n=12)和对照组(n=12),2组均通过条件恐惧箱构建条件恐惧模型。taVNS组每天接受1次taVNS(疏密波,2 Hz/15 Hz,强度2 mA,30 min),连续刺激6 d,对照组同时接受假taVNS(强度0 mA,其余参数同taVNS组)。在2次刺激后,检测场景线索恐惧记忆僵住时间百分比以及旷场实验的中心区活动总距离和总时间。在第4次和第6次刺激后,检测声音线索恐惧记忆僵住时间百分比。完成所有行为学检测后处死小鼠,测量脾脏指数,检测血清和脾脏中白细胞介素(IL)‑1β和IL‑10的水平。结果在2次刺激后,taVNS组的场景线索恐惧记忆僵住时间百分比低于对照组(10.7%±8.0%比25.8%±14.3%,P=0.004),而旷场实验的中心区活动总距离[(363.1±125.8)cm比(234.1±99.2)cm,P=0.011]和总时间[(39.0±14.7)s比(23.4±11.6)s,P=0.008]高于对照组。taVNS组的听觉恐惧记忆僵住时间百分比在第4次(36.4%±18.5%比58.4%±21.5%,P=0.013)和第6次(30.3%±20.7%比63.2%±26.6%,P=0.003)刺激后均低于对照组。taVNS组血清和脾脏中的IL‑1β均低于对照组(均P<0.05),且血清和脾脏中的IL‑10均高于对照组(均P<0.05)。结论taVNS可降低条件恐惧小鼠的恐惧记忆,伴随全身和脾脏炎症反应的改善,提示脾脏炎症反应可能与taVNS降低恐惧记忆作用有关。Objective To investigate the effect of transcutaneous auricular vagus nerve stimulation(taVNS)on fear memory and its regulatory role in splenic inflammatory responses in fear‑conditioned mice.Methods Twenty‑four 12‑week‑old healthy,male C57BL/6J mice were randomized into two groups using a random number table:taVNS(n=12)and control(n=12).Both groups underwent conditioned fear modeling using a fear conditioning chamber.The taVNS group received daily taVNS stimulation(dense‑disperse wave,2 Hz/15 Hz,intensity 2 mA,30 min)for 6 consecutive days, while the control group received sham taVNS (intensity 0 mA, with other parameters identical to the taVNS group). Following two stimulations, the freezing time percentage of contextual fear memory was assessed, along with total distance and time spent in the center zone of the open‑field test. After the 4th and 6th stimulations, the freezing time percentage of auditory‑cued fear memory was evaluated. Following all behavioral tests, mice were euthanized to measure the spleen index, and levels of interleukin (IL)‑1β and IL‑10 were measured in both the serum and spleen tissues. Results After two stimulations, the freezing time percentage of contextual fear memory in the taVNS group was lower than that of the control group (10.7%±8.0% vs 25.8%±14.3%, P=0.004), while the total distance [(363.1±125.8) cm vs (234.1±99.2) cm, P=0.011] and total time [(39.0±14.7) s vs (23.4±11.6) s, P=0.008] in the center zone of the open‑field test were higher in the taVNS group. The freezing time percentage of auditory‑cued fear memory was lower in the taVNS group compared to the control group after the 4th (36.4%±18.5% vs 58.4%± 21.5%, P=0.013) and 6th (30.3%±20.7% vs 63.2%±26.6%, P=0.003) stimulations. Serum and splenic IL‑1β levels were lower in the taVNS group compared to the control group (all P<0.05), while serum and splenic IL‑10 levels were higher in the taVNS group (all P<0.05). Conclusions This study indicates that taVNS reduces fear memory in fear‑c

关 键 词：恐惧 迷走神经(电)刺激 创伤后应激障碍 脾脏 炎症 

分 类 号：G63[文化科学—教育学]