【作者】 高博；

【导师】 孙广仁；

【作者基本信息】 山东中医药大学 ， 中医基础理论， 2009， 博士

【摘要】 目的:从理论上,对慢性阻塞性肺疾病(COPD)寒饮蕴肺证进行系统的阐释与论证,以丰富寒饮蕴肺证理论。利用熏烟、气管滴注脂多糖加寒凉刺激的方法复制慢性阻塞性肺疾病寒饮蕴肺证大鼠模型,并在此基础上用自拟温阳化饮方对该病证进行干预,从细胞分子水平观察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,反证COPD寒饮蕴肺证的病理机制,为防治该病证提供新思路和理论依据。方法:以自行研制的COPD寒饮蕴肺证大鼠模型为研究对象,在冬季将大鼠置于0℃冰箱中冷冻,饮水给以冰水混合物,配以熏烟、气管滴注脂多糖的方法,复制慢性阻塞性肺疾病寒饮蕴肺证大鼠模型,并用温阳化饮方干预。动态观察大鼠的一般情况、肺组织病理学改变,检测有关肺功能指标和血清白介素-8(IL-8)、白介素-10(IL-10),基质金属蛋白酶-9(MMP-9),组织金属蛋白酶抑制物-1(TIMP-1)。结果:慢性阻塞性肺疾病寒饮蕴肺证大鼠模型符合临床实际的理想病证结合动物模型应具备的造模要求,一般情况与寒饮蕴肺证的临床表现相符,各项指标的变化(除血清IL-8和IL-10外)也与慢性阻塞性肺疾病的指标变化相一致:大鼠体重减轻,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模型大鼠症状好转,肺功能改善,血清IL-8和血清IL-10浓度与慢性阻塞性肺疾病寒饮蕴肺证模型大鼠的相比无显著性变化(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:用本实验方法建立的慢性阻塞性肺疾病寒饮蕴肺证大鼠模型是符合临床实际的理想的病证结合动物模型,可在此基础上形成造模规范。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。更多还原

【Abstract】 Objective: This thesis expounds systematically the theoretic problems about the syndrome of accumulation of cold fluid in the lung in chronic obstructive pulmonary disease(COPD) to enrich the theory of the syndrome. The rat model with the syndrome of accumulation of cold fluid in the lung in COPD was established by inhalation cigarette,exposure to cold and intratracheal instillation of lipopolysaccharide(LPS) .Based on the pathologic rat models, observed the microcosmic mechanism by the pathologic rat models. Function developing change and promptly effect of the accumulation of cold fluid syndrome in the lung in COPD by stomach irritation with“Yang-Warming and Fluid-Dispersing Formula”were provided the mechanism to provide the thinking and theory to prevent and heal it.Methods: This research based on the rat models with the accumulution of cold fluid syndrom in the lung in COPD was set up with the methods of fleding with ice water with cold property in winter temperature 0℃in halation cigarette and intratracheal instillations of LPS and treatel with“Yang-Warming and Fluid-Dispersing Formula”. The observe the relevant indexes induding symptoms and signs pathological section of lung tissues,interleukin-8(IL-8) and interleukin-10(IL-10) in blood serum,MMP-9 and TIMP-1,and also the lung function measurements were carried out.Results: The results of the experiment showed that the development of pathologic rat models with the accumulation of cold fluid syndrome in the lung in COPD which proved to be repetitive is comparatively successful and reliable.The symptoms and signs of pathologic rat models with the accumulation of with clinical symptoms and signs of patients of the accumulation of cold fluid syndrome in the lung in COPD. The changes of microcosmic indexes coincided with those of COPD related to the syndrome. For example, the expressive index of avoirdupois were alleviated, dynamic lung compliance(Cldyn) decreased while inspiratory resistance(Ri) and expiratory resistance(Re) increased, lung tissues were inflammatorily damaged,IL-10 and IL-8 had no significant changes(P>0.05) comparing with the control group’s.The expression level of MMP-9,TIMP-1 and the result of MMP-9 than TIMP-1 increase.The symptoms and signs of pathologic rat models didn’t recover during the following 30 days by stoping the pathogeny.The remedy in the treated group ameliorated above indexes except IL-10 and IL-8 in blood serum,and the curative effect increased little by little.Conclusion: It is feasible to set up the rat models with the syndrome of accumulation of cold fluid in the lung in COPD which conformed to the case in clinical and can be developed the model standard.The mechanism of the accumulation of cold fluid syndrome in the lung in COPD may be increase the MMP-9 and TIMP-1 and disturb the balance of MMP-9/TIMP-1,especially the consequence of MMP-9 than TIMP-1.The symptoms and signs lung function and inflammatory reaction in airway of pathologic rat models could be a meliorared well by“Yang-Warming and Fluid-Dispersing Formula”.It means that we should treat it early and insistently.更多还原