“虚烦不得眠”证候的阐释:大鼠状态性焦虑及其睡眠时相变化  

Explanation of Syndrome of ‘Insomnia due to Deficient Dysphoria’ in Terms of Changes in State-Trait Anxiety and Sleep Phases

作　　者：杨悦 王艳艳[1] 卞宏生[1] 于爽[1] 李廷利[1] 黄莉莉[1] YANG Yue;WANG Yanyan;BIAN Hongsheng;YU Shuang;LI Tingli;HUANG Lili(Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学药学院,黑龙江哈尔滨150040

出　　处：《中医药学报》2022年第5期16-23,共8页Acta Chinese Medicine and Pharmacology

基　　金：国家自然科学基金资助项目(81274114,82003974);黑龙江省自然科学基金资助项目(LH2019H106,LH2020H098);黑龙江中医药大学博士创新科研基金项目(2015bs08)。

摘　　要：目的:“虚烦不得眠”是酸枣仁汤的主治证候。利用现代生物学理论与方法,阐明其病理变化的实质,复制相应的证候模型,为开展酸枣仁汤的中药药理研究奠定方法学基础。方法:选取SD雄性大鼠16只,在麻醉和脑立体定位条件下进行大鼠皮层脑电电极与肌电电极的埋置,手术恢复7 d后,将大鼠置于条件性恐惧刺激箱中,进行连续4 d状态性焦虑模型的复制,分别观测状态性焦虑大鼠高架十字迷宫(elevated plus maze, EPM)中第1、7、10、14、21天行为参数和脑电图(electroencephalogram, EEG)的变化。结果:与对照组相比,造模后大鼠僵直反应时间明显延长(P<0.01);EPM中开放臂运动时间和时间%于第1、7和10天显著缩短(P<0.05),进入开放臂次数和次数%于第1、7、10、14天显著降低(P<0.05),总入臂次数于第1、7、10、21天显著减少(P<0.05);与对照组相比,状态性焦虑大鼠的Wake时间明显延长(P<0.01,P<0.05),NREMS时间明显缩短(P<0.01,P<0.05),REMS时间明显增加(P<0.01,P<0.05),其中第1、7、10和14天大鼠觉醒-睡眠时间的变化更加显著;Wake时间比例于第7、10、14天明显增加(P<0.01,P<0.05),伴有NREMS时间比例第1、7、10、14天明显减少(P<0.01,P<0.05),REMS时间比例第1天的明显增加(P<0.05)。结论:“虚烦不得眠”证候的生物学基础为状态性焦虑及其并发的睡眠时相障碍。Objective: ‘Insomnia due to deficient dysphoria’ is the main indication of Suanzaoren Decoction. By using modern biological theories and methods, this study clarified the essence of its pathological changes, established the corresponding syndrome model, and laid a methodological foundation for the development of the pharmacological research of Suanzaoren Decoction. Methods: 16 male SD rats were selected, and EEG and EMG electrodes were embedded under the conditions of anesthesia and stereotaxic. After 7 days of recovery from the operation, the rats were placed in the conditioned fear stimulus box to replicate the state-trait anxiety model for 4 consecutive days. The behavioral parameters of EPM and EEG changes on 1 d, 7 d, 10 d, 14 d and 21 d were observed in the rats with state-trait anxiety, respectively. Results: Compared with those in the control group, the freezing time of the rats was significantly prolonged after modeling(P<0.01);time spent in open arms and time % in EPM were significantly shorter on 1 d, 7 d and 10 d(P<0.05), and the number of open arm entries and the entries % were significantly lowered on 1 d, 7 d, 10 d and 14 d(P<0.05). The total number of arm entries significantly reduced on 1 d, 7 d, 10 d and 21 d(P<0.05). Compared with those in the control group, Wake time of the rats with state-trait anxiety was significantly prolonged(P<0.05, P<0.01), NREMS time was significantly shortened(P<0.05, P<0.01), and REMS time was significantly increased(P<0.05, P<0.01), among which the changes in awaking-sleep time on 1 d, 7 d, 10 d and 14 d were more significant. The proportion of Wake time increased significantly on 7 d, 10 d and 14 d(P<0.05, P<0.01), there was a significant decrease in NREMS % on 1 d, 7 d, 10 d and 14 d(P<0.05, P<0.01), and there was a significant increase in REMS % on 1 d(P<0.05). Conclusion: The biological basis of the syndrome of ‘insomnia due to deficient dysphoria’ is state-trait anxiety and its concurrent sleep phase disorder.

关 键 词：虚烦不得眠 状态性焦虑 睡眠时相 EEG EPM 

分 类 号：R274.97[医药卫生—中西医结合]