卫气与神经-免疫-内分泌调节对酒五味子促睡眠的节律调控作用研究

Wine-Schisandra chinensis (WSC), as a common processed product, applied for palpitation and insomnia with the traditional comparative advantage in sleep therapy. Former researches had showed that WSC had significant advantages in therapeutic material basis related to sleep and pharmacokinetics, and its exact promoting sleep efficiency exhibiting overall effect of multiple pathways and multiple targets which was not only localized in the central nervous system. Therefore, in competition with sedative hypnotic drugs, the treatment characteristics of WSC need to be carried forward according to the traditional Chinese medicine theory, and the mechanism should be clarified with its superiority and strengths. Based on the existing research foundation, in this study, the general framework of chemical drugs for insomnia will be broken. Firstly according to the theory of circulation of Defensive Qi, around sleep wake rhythm, the novel idea of neural-endocrine-immune network regulation is adopted, which is highly correlated to circulation of Defensive Qi with holism and circadian rhythm. Regulation of physiological rhythm of WSC could be clarified systematically, and the clinical treatment features of WSC can be manifested. Meanwhile, research technique and reasonable evaluation method for TCM and their processed products in sleep promoting effect will form which could render scientific support and theoretical basis for tranquillization TCM in evaluation of efficacy, mechanism and clinical application.

酒五味子为五味子常用炮制品，在心悸失眠治疗中具有传统优势。课题组前期研究结果显示酒五味子在睡眠相关药效物质基础、药代动力学方面，具有优于木脂素类单体化合物或其混合物的显著优势。其确切的促睡眠功效，不仅仅局限在中枢神经系统上，而是呈现多途径多靶点的整体作用。因此，在与镇静催眠类药品的竞争中，要发扬酒五味子治疗特色，就需要依据中医药理论阐明机制，充分展示出其独到之处。本课题拟在前期基础上，打破化学药物治疗失眠研究思路，首次根据卫气循行理论、围绕睡眠-觉醒节律、采用整体作用观、节律周期与卫气高度相关的神经-内分泌-免疫网络调控新思路，进一步阐述酒五味子生理节律调控作用，彰显其在失眠症方面的治疗特色，为这一古老炮制品种在睡眠障碍治疗中占据坚实的一席之地。同时，形成适合于中药及其炮制品在促睡眠功效研究中的技术与合理评价方法，为安神中药的药效评价、机制阐述、临床应用规范，提供科学支撑和理论依据。

本课题探索建立了慢性失眠模型，聚焦神经-内分泌-免疫网络，通过靶向代谢组学、分子生物学，结合EEG脑电、ECG心电分析，发现五味子和酒五味子影响神经内分泌系统HPA轴，参与心血管系统的调节，改善睡眠同时缓解与失眠相关的心血管功能障碍。与褪黑素相比，生、酒五味子在延长NREM周期改善睡眠质量方面表现更显著。二者增加了下丘脑MT1受体的表达，并调节了Bmal1、Clock、Per2的昼夜节律表达水平。通过上述研究内容的积极开展，完成了生、酒五味子对睡眠时相作用特征及其促睡眠作用优势的首次阐述，为中药多靶点多途径的中枢疾病防治提供科学依据。