经皮耳穴-迷走神经刺激对抑郁症模型大鼠前额叶皮质Toll样受体4/髓样分化因子88信号通路相关蛋白表达的影响  

Effect of transcutaneous auricular vagus nerve stimulation on the expression of TLR4、MyD88、IL-18 protein in the prefrontal cortex of depression rats

作　　者：王艺霏 王瑜 张悦 国笑 何勋[1] 张金铃[1] 荣培晶[1] WANG Yi-fei;WANG Yu;ZHANG Yue;GUO Xiao;HE Xun;ZHANG Jin-ling;RONG Pei-jing(Department of Physiolo-gy,Institute of Acupuncture and Moxibustion,China Academy of Chinese Medical Sciences,Beijing 100700)

机构地区：[1]中国中医科学院针灸研究所机能研究室,北京100700

出　　处：《针刺研究》2021年第7期580-585,共6页Acupuncture Research

基　　金：国家重点研发计划(No.2018YFC1705800);国家自然科学基金项目(No.81803872)。

摘　　要：目的:观察经皮耳穴-迷走神经刺激(taVNS)对抑郁症模型大鼠抑郁样行为的改善作用,探讨其可能的分子机制。方法:24只SD大鼠随机分为空白组、模型组、耳缘-非迷走神经刺激(tnVNS)组、经皮耳穴-迷走神经刺激(taVNS)组。通过连续35 d慢性不可预知温和刺激结合孤养制备抑郁症大鼠模型,造模14 d后,分别于每天应激前1 h在taVNS组和tnVNS组大鼠双侧耳甲腔/耳缘进行电刺激,强度2 mA,频率2 Hz/15 Hz,每次干预30 min,持续21 d。记录造模前以及每周各组大鼠体质量增加量、强迫游泳不动时间。实验结束后采用Western blot法检测各组大鼠前额叶皮质中Toll样受体4(TLR4)、髓样分化因子88(MyD88)和白细胞介素(IL-18)的蛋白相对表达量。结果:造模14 d后,与空白组比较,模型组大鼠体质量增加量显著降低(P<0.01),强迫游泳不动时间显著增加(P<0.01),前额叶皮质TLR4、MyD88、IL-18相对表达量显著升高(P<0.01)。干预21 d后,与模型组比较,taVNS组大鼠体质量增加量显著升高(P<0.01),taVNS组、tnVNS组大鼠游泳不动时间显著减少(P<0.01),前额叶皮质TLR4、MyD88、IL-18蛋白表达显著降低(P<0.01)。结论:taVNS可改善大鼠抑郁样行为,其机制可能与抑制前额叶皮质中TLR4/MyD88信号通路介导的炎性反应有关。Objective To observe the effect of transcutaneous auricular vagus nerve stimulation(taVNS)on the depressive behavior in depression rats,so as to explore its mechanism underlying improvement of depression.Methods A total of 24 male Sprague Dawley rats were randomly divided into normal,depression model,taVNS,tnVNS(transcutaneous auricular none-vagus nerve stimulaton)groups(n=6 in each group).The depression model was established by chronic unpredictable mild stimulation combined with solitary raising for 35 consecutive days.After 14 days modeling,transcutaneous electrostimulation(2 mA,2 Hz/15 Hz)was applied to auricular concha or auricular margin,respectively.Each intervention was conducted for 30 minutes,once daily for 21 days.The depression-like behavior was evaluated by forced swimming immobility time and body weight.The expression levels of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88)and interleukin-18(IL-18)protein in the prefrontal cortex were detected by Western blot.Results Following modeling,the increase amount of body weight was decreased,the forced swimming immobility time and expression TLR4,MyD88 and IL-18 protein in the prefrontal cortex were increased in the model group than those in the normal group(P<0.01).Following the treatment and compared with the model group,the increase amount of body weight in the taVNS group was obviously increased(P<0.05),the swimming immobility time and the expression of TLR4,MyD88,IL-18 protein in the taVNS and tnVNS groups were significantly decreased(P<0.01).Conclusion TaVNS is able to improve depression in depression rats,which is probably related to its effect in inhibiting inflammatory response of TLR4/MyD88 signaling pathway in prefrontal cortex.

关 键 词：经皮耳穴-迷走神经刺激 抑郁症 TLR4/MyD88信号通路 

分 类 号：R246.6[医药卫生—针灸推拿学]