基于干旱环境影响大鼠慢性支气管炎病变过程的西北燥证证候机制研究

Northwest Dryness Syndrome is the symbolic regional syndrome caused by aridity and sand storm environment. It has been proved by epidemiological investigation and case-control study that NDS is the important risk factors for sub-health state in Chinese northwest region, which also can make common and frequently-occurring disease happen and aggravate. So it is very important for us to prevent NDS for the sale of improving regional people’s health level..Basing on the characteristics of close association with NDS, similar etiology and lesion site, the study chooses chronic bronchitis as the carrier for disease-syndrome combination. Using programmable artificial climate box, sand dust experiment box and other equipment, control laboratory factors，such as dust, blowing, temperature, relative humidity to create an man-made environment of northwest drought and sandstorm, and to observe the different special environment influence to healthy and chronic bronchitis rats. Still, make respiratory function as the mediation to find the intrinsic association between syndrome differentiation result and micro experiment indicators change. By this way to analyze and deduce NDS’s micro syndrome mechanism. From the view of Pharmacology, the results will be improved by the comparative effectiveness research of therapeutic intervention, including lung-nourish prescription perfusion, dexamethasone perfusion, lung-nourish prescription combined dexamethasone perfusion.

西北燥证是区域性干旱所致之标志性方域病证，流行病学研究和病例对照研究分别证实该证是西北地区人群亚健康及诱发和加重区域性常见病的危险要素，防治该证对提高区域人群健康水平有十分重要的意义。本研究紧扣现代医学疾病与西北燥证病证关联紧密、病因相似、病位趋同之特性，选择慢性支气管炎为病证结合研究对象，运用程控人工气候箱、砂尘实验箱等，调控沙尘、吹风、温度、相对湿度等实验室施加因素，营造西北干旱风沙环境，观察特殊环境对健康大鼠和气道滴脂多糖合烟熏所建慢性支气管炎病鼠模型的影响，并以呼吸功能测定结果为桥梁，寻找西北燥证辨证结果与微观指标变化间的内在联系，研究干旱是否可致西北燥证为主的亚健康状态，探索干旱对机体免疫屏障及其功能的损害是否为西北燥证的证候机制；并据清肺润燥剂、地塞米松、清肺润燥剂联合地塞米松干预特殊环境下慢性支气管炎病鼠之对比研究结果，从方药学出发反证所探求之西北燥证微观证候机制的科学性。

西北燥证是以感受燥邪为主因以口鼻咽喉、肌肤干燥等不适症状为特征的复合型中医证候，罹患此证是西北地区人群亚健康状态、特高发疾病(如慢性支气管炎)发病和病情加重的诱因，探索其微观证候机制将助力于客观阐释燥邪致病机制、科学预防干旱环境亚健康及防治西北地区特高发疾病。.本项目通过探究中医理论、分析气象数据、完成动物实验，建立并验证燥邪(秋燥之邪和西北方域燥邪)实验室模拟方案，确立从秋燥之邪和西北方域燥邪微观致病机制的比较研究中探寻西北燥证证候机制之研究思路。基于研究项目组发现暴露性器官腺体形态学改变(泪腺腺泡萎缩等)、肺系和暴露性器官固有免疫蛋白含量变化(肺和气道SP-D表达增强、泪腺和鼻黏膜DB-2异常表达)、免疫亢进(外周血CD4+/CD8+值异常升高)、肺组织TNF-α表达增强、气道阻力增加、BALF中出现RBC等是燥邪引发亚健康的机制，且虽秋燥之邪和西北方域燥邪致病机制不尽相同，但健康机体对此具有习服能力。. 不同于秋燥之邪，西北方域燥邪可通过引发持续免疫亢进，加重炎性反应(血清TNF-α水平升高)，增加单位体积BALF中RBC数，升高气道阻力，降低小气道通气功能和探究行为能力等影响大鼠慢性支气管炎病变过程。较之于地塞米松、地塞米松联合西北燥证经验方，单纯应用经验方可通过加速呼吸频率、增加潮气量、缓解小气道阻塞并改善其通气功能、消除BALF中RBC、降低BALF中Neu%，升高Eos %，改善炎性反应并负向调节Ⅰ超敏反应，从而发挥宣肺润燥之效，对燥邪干预下慢性支气管炎疗效更佳。. 此外，肺组织AQP-5和气道AQP-3表达与燥邪干预不相关，故免疫亢进、黏膜屏障受损、固有免疫蛋白DB-2、SP-D等异常表达、炎性反应增强是西北燥证微观机制之一，此为基于病因辨证联合暴露性器官(目鼻、气道等)黏膜组织病理及蛋白差异表达等建立和评价西北燥证动物模型提供依据。