基于“治痰即治呆”理论探讨党参-茯苓配伍调控痴呆症脑水液代谢的作用机理

痴呆症已成为威胁全球老年人身体健康的重大疾病，其复杂的发病机制和药物研发困难是目前面临的重大挑战。新近的研究发现BBB完整性破坏和胶质淋巴系统功能紊乱是导致痴呆症的关键环节，这与中医“治痰即治呆”对痴呆症的认识和治疗方略高度一致。党参茯苓配伍是治疗脾胃病的常见药对，具有益气健脾、利水渗湿和宁心安神功效，前期研究显示它能够明显降低痴呆模型大鼠BBB通透性和脑含水量，这为本项目“党参茯苓配伍通过维持BBB完整性和调控胶质淋巴系统调节水液代谢，促进脑内代谢废物清除而改善痴呆症”的工作假说提供了依据。故本研究以2-VO模型大鼠和APP/PS1转基因小鼠为研究载体，应用UPLC-TOF-MS/MS、荧光共定位、尿液代谢组学等多种技术手段，以调控胶质淋巴系统的AQP4极化（水液代谢）为主线，入血入脏器化学成分分析为辅，从物质基础、作用靶器官组织和作用途径多角度阐释“治痰即治呆”的现代科学内涵。

Dementia has become a major threat to the health of the elderly in the world. Its complex pathogenesis and difficult drug development are major challenges. Recent studies have found that BBB integrity damage and glymphatic system dysfunction are the key links leading to dementia, which is highly consistent with the understanding and treatment strategy of “treating Tan is treating dementia” in traditional Chinese medicine. The compatibility of Dangshen and Fuling is a common couplet medicinals for the treatment of Piand stomach diseases, which has the effects of supplementing Qi and strengthening Pi, clearing damp and promoting diuresisand tranquilizing the mind. Previous studies have shown that it can significantly reduce BBB permeability and brain water content of dementia model rats, which provides a support for the hypothesis of this work thatcompatibility of Dangshen and Fuling can improve brain function by maintaining BBB integrity and regulating glymphatic system, regulating the fluid metabolism and promoting the elimination of metabolic wastes in the brain. Therefore, in this study, 2-VO model rats and APP/PS1 transgenic mice were used as the research vectors, UPLC-TOF-MS/MS, fluorescence colocalization, urine metabonomics and other technical methods were applicated to explaine the modern scientific connotation of “treating Tan is treating dementia” from multiple perspectives including the material basis, target organs and pathways with the regulation of AQP4 polarization (fluid metabolism) of glymphatic system as the main line and chemical composition analysis of blood and organs as supplement.