Li Yujie, Wei Dandan, Zhang Minghao, Yue Tiantian, Du Huimin, Liu Qi, Gan Shihu, Liu Hanbin, Dong Yijie, Qiao Xinyue, Zhang Yichi, Yang Liping
Pharmacology Laboratory, School of Basic Medical Medicine, Zhengzhou, P. R. China.
College of First Clinical Medical, Henan, University of Chinese Medicine, Zhengzhou, Henan 450046, P.R. China.
Curr Pharm Biotechnol. 2022;23(8):1080-1093. doi: 10.2174/1389201022666211012102501.
Sleep curtailment is a serious problem in many societies. Clinical evidence has shown that sleep deprivation is associated with mood dysregulation, formation of false memory, cardio-metabolic risk factors and outcomes, inflammatory disease risk, and all-cause mortality. The affective disorder dysregulation caused by insufficient sleep has become an increasingly serious health problem. However, to date, not much attention has been paid to the mild affective dysregulation caused by insufficient sleep, and there is no clear and standard therapeutic method to treat it. The Xiaoyao Pill is a classic Chinese medicinal formula, with the effect of dispersing stagnated hepatoqi, invigorating the spleen, and nourishing the blood. Therefore, it is most commonly used to treat gynecological diseases in China. In the present study, the effects of the Xiaoyao Pill on affective dysregulation of sleep-deprived mice and its underlying molecular mechanisms were investigated.
Forty adult female mice were used in the present study. The sleep deprivation model was established by improving the multi-platform water environment method. After 7 consecutive days of sleep deprivation, the mice were administrated low (LXYP, 0.32mg/kg) and high (HXYP, 0.64 mg/kg) doses of the Xiaoyao Pill for two weeks. Then, the body weight, behavioral deficits, and histopathology were evaluated. Meanwhile, the expression of c-fos protein and the concentrations of monoamine neurotransmitters in the hippocampus and prefrontal cortex were determined after two weeks of treatment.
Xiaoyao Pill treatment significantly increased body weight and sucrose consumption and decreased the irritability scores of the sleep-deprived mice. Meanwhile, Xiaoyao Pill treatment prevented brain injury and inhibited the expression of c-fos protein in the hippocampus and prefrontal cortex. In addition, HXYP treatment significantly upregulated the levels of NE in the hippocampus and prefrontal cortex (p < 0.01). LXYP treatment significantly up-regulated the levels of 5-HT in the prefrontal cortex. Meanwhile, both HXYP and LXYP treatment significantly upregulated the levels of DA in the prefrontal cortex (p < 0.05 or p < 0.01) of sleep-deprived mice.
The present study demonstrates that Xiaoyao Pill treatment prevented the behavioral deficits of mice induced by sleep deprivation by promoting the recovery of brain tissue injury and up-regulating the levels of NE, 5-HT, and DA in the brain tissue.
睡眠减少在许多社会中都是一个严重问题。临床证据表明，睡眠剥夺与情绪失调、错误记忆形成、心血管代谢危险因素及后果、炎症性疾病风险和全因死亡率相关。睡眠不足引起的情感障碍失调已成为一个日益严重的健康问题。然而，迄今为止，睡眠不足引起的轻度情感失调尚未得到足够关注，且尚无明确标准的治疗方法。逍遥丸是一种经典的中药方剂，具有疏肝理气、健脾养血的功效。因此，在中国它最常用于治疗妇科疾病。在本研究中，探讨了逍遥丸对睡眠剥夺小鼠情感失调的影响及其潜在分子机制。
本研究使用了40只成年雌性小鼠。通过改良多平台水环境法建立睡眠剥夺模型。连续7天睡眠剥夺后，给小鼠连续两周给予低剂量（LXYP，0.32mg/kg）和高剂量（HXYP，0.64mg/kg）的逍遥丸。然后，评估体重、行为缺陷和组织病理学。同时，在治疗两周后测定海马和前额叶皮质中c-fos蛋白的表达以及单胺类神经递质的浓度。
逍遥丸治疗显著增加了睡眠剥夺小鼠的体重和蔗糖消耗量，并降低了其易怒评分。同时，逍遥丸治疗预防了脑损伤，并抑制了海马和前额叶皮质中c-fos蛋白的表达。此外，HXYP治疗显著上调了海马和前额叶皮质中NE的水平（p<0.01）。LXYP治疗显著上调了前额叶皮质中5-HT的水平。同时，HXYP和LXYP治疗均显著上调了睡眠剥夺小鼠前额叶皮质中DA的水平（p<0.05或p<0.01）。
本研究表明，逍遥丸治疗通过促进脑组织损伤的恢复和上调脑组织中NE、5-HT和DA的水平，预防了睡眠剥夺诱导的小鼠行为缺陷。
