Wang Mengyuan, Li Bo, Liu Yijiang, Zhang Mengting, Huang Caoxin, Cai Teng, Jia Yibing, Huang Xiaoqing, Ke Hongfei, Liu Suhuan, Yang Shuyu
Research Studio of Traditional Chinese Medicine, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Front Pharmacol. 2023 Feb 6;14:1107507. doi: 10.3389/fphar.2023.1107507. eCollection 2023.
Sleep disorders are common clinical psychosomatic disorders that can co-exist with a variety of conditions. In humans and animal models, sleep deprivation (SD) is closely related with gastrointestinal diseases. Shu-Xie Decoction (SX) is a traditional Chinese medicine (TCM) with anti-nociceptive, anti-inflammatory, and antidepressant properties. SX is effective in the clinic for treating patients with abnormal sleep and/or gastrointestinal disorders, but the underlying mechanisms are not known. This study investigated the mechanisms by which SX alleviates SD-induced colon injury . C57BL/6 mice were placed on an automated sleep deprivation system for 72 h to generate an acute sleep deprivation (ASD) model, and low-dose SX (SXL), high-dose SX (SXH), or S-zopiclone (S-z) as a positive control using the oral gavage were given during the whole ASD-induced period for one time each day. The colon length was measured and the colon morphology was visualized using hematoxylin and eosin (H&E) staining. ROS and the redox biomarkers include reduced glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) were detected. Quantitative real-time PCR (qRT-PCR), molecular docking, immunofluorescence and western blotting assays were performed to detect the antioxidant signaling pathways ASD significantly increased FBG levels, decreased colon length, moderately increased the infiltration of inflammatory cells in the colon mucosa, altered the colon mucosal structure, increased the levels of ROS, GSH, MDA, and SOD activity compared with the controls. These adverse effects were significantly alleviated by SX treatment. ASD induced nuclear translocation of NRF2 in the colon mucosal cells and increased the expression levels of p62, NQO1, and HO1 transcripts and proteins, but these effects were reversed by SX treatment. SX decoction ameliorated ASD-induced oxidative stress and colon injury by suppressing the p62/KEAP1/NRF2/HO1/NQO1 signaling pathway. In conclusion, combined clinical experience, SX may be a promising drug for sleep disorder combined with colitis.
睡眠障碍是常见的临床身心疾病，可与多种病症共存。在人类和动物模型中，睡眠剥夺（SD）与胃肠道疾病密切相关。舒泻汤（SX）是一种具有抗伤害感受、抗炎和抗抑郁特性的中药。SX在临床上对治疗睡眠异常和/或胃肠道疾病患者有效，但其潜在机制尚不清楚。本研究探讨了SX减轻SD诱导的结肠损伤的机制。将C57BL/6小鼠置于自动睡眠剥夺系统上72小时以建立急性睡眠剥夺（ASD）模型，并在整个ASD诱导期内每天一次通过口服灌胃给予低剂量SX（SXL）、高剂量SX（SXH）或作为阳性对照的佐匹克隆（S-z）。测量结肠长度并使用苏木精和伊红（H&E）染色观察结肠形态。检测活性氧（ROS）以及氧化还原生物标志物，包括还原型谷胱甘肽（GSH）、丙二醛（MDA）和超氧化物歧化酶（SOD）。进行定量实时聚合酶链反应（qRT-PCR）、分子对接、免疫荧光和蛋白质印迹分析以检测抗氧化信号通路。与对照组相比，ASD显著增加空腹血糖（FBG）水平，缩短结肠长度，适度增加结肠黏膜中炎性细胞浸润，改变结肠黏膜结构，增加ROS、GSH、MDA水平以及SOD活性。SX治疗可显著减轻这些不良反应。ASD诱导结肠黏膜细胞中核因子E2相关因子2（NRF2）核转位，并增加p62、醌氧化还原酶1（NQO1）和血红素加氧酶1（HO1）转录本和蛋白质的表达水平，但这些作用被SX治疗逆转。舒泻汤通过抑制p62/ Kelch样ECH相关蛋白1（KEAP1）/NRF2/HO1/NQO1信号通路改善ASD诱导的氧化应激和结肠损伤。总之，结合临床经验，SX可能是治疗睡眠障碍合并结肠炎的一种有前景的药物。
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