哮喘气道黏液流变行为变化及其影响因素和临床意义的研究

Airway mucus is an important defense barrier for airways and lung, which traps exogenous hazardous particulate matters and excludes them out of body via beating of the cilia and coughing, but selectively allows passage of beneficial matters. This precise defense function in normal physiological state largely relies on appropriate rheological properties of the airway mucus. In asthma, the patient's mucus is highly viscous with abnormal rheological behaviors, which causes impaired flow of the mucus and in worse cases form mucus plug (sputum plug) to obstruct the airway or even threaten life. However, mechanisms of the rheological alteration in asthmatic airway mucus is not clear. Thus, we propose in regards of normal and asthmatic airway mucus to 1) characterize and analyze mucus compositions (esp. mucin, inflammatory cells) and their changes; 2) use multiple methods to systematically investigate bulk and micro-rheological behaviors and their determinants; 3) examine microscopic characteristics of the mucus in relation to its composition; 4) establish constitutive equations and corresponding numerical simulation method for mucus rheology; 5) reveal the influence of mucus rheology on transportation of particulate matters. This study may provide scientific basis for further understanding altered rheological behaviors of asthmatic airway mucus and their implications to clinical diagnosis and treatment as well as evaluation of drug delivery, and may also provide new ideas for related asthma therapy.

气道黏液是气道及肺的重要保护屏障，它阻挡外来有害颗粒物并通过纤毛摆动与咳嗽将有害颗粒物排出体内，而让有益物质选择性通过。这些精确的保护功能在很大程度上依赖于正常生理条件下气道黏液合适的流变特性。哮喘患者气道黏液粘稠度增高，流变行为异常导致黏液流动不畅，严重情况下形成黏液栓（痰栓），阻塞气道甚至危及生命。然而，哮喘气道黏液流变性质和行为改变的机理还不清楚。因此，本项目拟针对正常人与哮喘患者的气道黏液：1）表征和分析黏液的组分（特别是黏液蛋白，炎症细胞）及其变化，2）研究黏液组分变化对其微观结构的影响；3）综合多种手段，研究黏液宏观和微观流变行为特征及其影响因素；4）考察黏液流变行为对其中颗粒物输运的影响；5）建立黏液流变本构方程的数值模型和颗粒物运动模拟方法。本项目为深入理解哮喘黏液流变学变化的机理及其对临床诊断和治疗、药物输运评价等的意义提供科学依据，为探索相应的哮喘治疗方法提供新思路。

气道黏液是存在于气道内壁表面的一层富含黏蛋白的黏弹性流体，其流变特性在哮喘和新冠肺炎等呼吸疾病的病理机制和临床诊治中具有十分重要的作用。本项目采用不同含量的黏蛋白溶液作为正常与哮喘病理气道黏液的模型，系统地研究了这些黏液模型的流变行为及其影响因素和变化机理，并获得了一些重要的研究结果，包括：1）黏蛋白通过聚集与自组装等行为构成黏液微观网络结构；2）气道黏液流变学行为的四参数Burgers模型及其“剪切稀化”流变行为特征；3）细微颗粒物对气道黏液流变特性的影响，其中，大气污染物PM2.5改变黏液微观网络结构的网格大小使其黏度显著升高，而Fe2O3纳米颗粒则破坏黏液的微观网络结构使其黏度显著降低，这为哮喘患者预防雾霾天气的危害和开发新型物理降黏药物提供了科学依据；4）利用低频振荡剪切应变显著降低黏液黏度的原理开发一种用于清除气道黏液的低频强迫振荡压力波化痰排痰技术。这些研究结果对预防和治疗哮喘等气道黏液高分泌呼吸道疾病及其药物输运评价等方面具有重要的参考价值，为探索新颖的化痰排痰方法和技术提供了思路。