慢性阻塞性肺疾病寒饮蕴肺证大鼠模型病理机制的初步研究

A Preliminary Research on the Pathological Mechanism of Chronic Obstructive Pulmonary Disease (COPD) by Using Rat Model with Syndrome of Accumulation of Cold Fluid in the Lung

目的:从细胞分子水平观察慢性阻塞性肺疾病(COPD)寒饮蕴肺证发展、变化的动态病理机制,以及温阳化饮方对COPD寒饮蕴肺证的干预作用、动态变化及时效性。方法:采用随机对照、动物造模的方法。结果:慢性阻塞性肺疾病寒饮蕴肺证大鼠模型体重减轻,吸气阻力和呼气阻力升高、肺顺应性下降,但血清IL-8浓度和血清IL-10浓度与正常组相比无显著性变化(P>0.05),MMP-9、TIMP-1表达水平及MMP-9/TIMP-1比值升高,病理切片显示肺组织出现炎性损伤和肺纤维化改变。在撤除造模因素后30天内,模型大鼠的一般情况及各项指标没有明显好转,且在20天以后出现急速恶化。用温阳化饮方干预的大鼠症状好转,肺功能改善,血清IL-8和血清IL-10浓度与COPD寒饮蕴肺证模型大鼠相比无显著性变化,MMP-9、TIMP-1表达水平及MMP-9/TIMP-1比值下降,病理切片示炎性损伤明显减轻;初期即见疗效,中期一度治疗进展缓慢,后期疗效显著。结论:MMP-9的增多引起了TIMP-1反馈性升高与MMP-9/TIMP-1失衡,尤其是此比值的过度升高,可能是COPD寒饮蕴肺证发生的重要机制。该病证在病变形成以后呈渐进性发展,温阳化饮方在改善模型大鼠的一般情况、肺功能和抑制气道炎症反应方面有比较肯定的疗效;早期治疗和长期坚持治疗有着积极的意义。

Objective： This research aims at the dynamic pathological mechanism of COPD with accumulation of cold fluid in the lung on the cellular and molecular level,and the intervention effect of yang-warming and fluid-dispersing formula on COPD,as well as the dynamic development and time effectiveness of this formula on COPD.Method： Randomized controlled trial and animal model were applied.Result： The rat model with syndrome of accumulation of cold fluid in the lung showed weight loss,inspiratory resistance and expiratory resistance increase,and pulmonary compliance decrease,but the serum IL-8 and IL-10 showed no obvious difference compared to the control group（P0.05）,while the MMP-9 and TIMP-1 expression level and MMP-9/TIMP-1 became high.Also pathological sections showed inflammatory lesions and fibrosis of lung tissues.30 days after removing the stimulatory factors making animal models,the rat model showed no improvement of systemic condition and relevant parameters,which deteriorated rapidly after 20 days.After using the yang-warming and fluid-dispersing formula,lung function improved and the expression level of MMP-9 and TIMP-1and MMP-9/TIMP-1 decreased,and pathological sections showed alleviation of inflammatory lesions.The formula exhibited the therapeutic effect in the early stage,retarded effect in the middle stage,and obvious effect in the later stage.Conclusion： The increase of MMP-9 leads to the TIMP increase due to the feedback effect,and the imbalance between MMP-9 and TIMP-1,especially the excessive increase of MMP-9/TIMP-1,which may be an important factor to cause COPD,which manifests as a progressive development after its formation.The yang-warming and fluid-dispersing formula can improve the systemic condition and lung function,and inhibit the inflammatory reaction of airway,this formula can be used at the early stage and for long duration in the treatment of COPD.