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目的 制备大鼠慢性阻塞性肺疾病 (COPD)模型 ,探讨气道细胞外基质 (ECM)重塑的病理特点及其在气流阻塞中的作用 ,以及不同干预因素的影响。方法 熏香烟加气管注入小量内毒素法建立大鼠COPD模型 ,观察气道重塑的病理特点 ,测定肺功能及血气、气道各层横截面积 ,支气管肺组织匀浆羟脯氨酸 (Hy)含量 ;粘膜下成纤维细胞 (Fb)、淋巴细胞及肺泡巨噬细胞计数 ;放射免疫法测定血清中透明质酸、层粘连素含量。观察蛋白激酶C抑制剂H7、氧自由基清除剂N 乙酰半胱氨酸(NAC)和转化生长因子 (TGF) β单抗干预对大鼠模型气道重塑的影响。 结果 所建模型的病理及病理生理学改变基本符合人类COPD特点 ,I型胶原为主的ECM气道壁过度沉积 ;小支气管上皮层、平滑肌层截面积 (各为 2 1114 μm2 、16 0 6 1μm2 )与对照组 (各为 130 5 6 μm2 及 6 6 92 μm2 )比较 ,差异有显著性 (P均 <0 .0 0 1)。NAC组、H7组及TCF β单抗组上皮层截面积分别为 12 70 1μm2 、11836 μm2 及112 4 4 μm2 ;平滑肌层截面积分别为 70 5 1μm2 、6 4 2 6 μm2 及 6 4 2 0 μm2 ,与模型组比较差异有显著性(P均 <0 0 0 1)。模型组粘膜下Fb数为 13.6± 4 .2 ,对照组为 6 .8± 1.4 ,且功能活跃 ,淋巴细胞及肺泡巨噬细胞数亦显著增高。NAC组及TGF ?
OBJECTIVE: To establish a rat model of chronic obstructive pulmonary disease (COPD) and investigate the pathological characteristics of airway extracellular matrix (ECM) remodeling and its role in airflow obstruction as well as the influence of different interventions. Methods The model of COPD was established by injecting a small amount of lipopolysaccharide (LPS) into the cigarette and adding a small amount of endotoxin into the trachea to observe the pathological characteristics of the airway remodeling. The lung function, blood gas and airway cross-sectional area, Hy) content; submucosal fibroblasts (Fb), lymphocytes and alveolar macrophages count; radioimmunoassay determination of serum hyaluronic acid, laminin levels. To observe the effects of protein kinase C inhibitor H7, oxygen free radical scavengers NAC and TGFβ on airway remodeling in rat models. Results The pathological and pathophysiological changes of the established model were basically consistent with the characteristics of human COPD. The type I collagen-dominated ECM airway wall was over-deposited. The area of small bronchial epithelium and smooth muscle layer (2 1114 μm 2 and 16 0 6 1 μm 2 respectively) Compared with the control group (each 130 5 6 μm 2 and 6 6 92 μm 2), the difference was significant (P <0.01). The cross-sectional areas of epithelial layer of NAC group, H7 group and TCF β monoclonal antibody group were 12 70 1μm2, 11836 μm2 and 112 4 4 μm2, respectively. The cross-sectional area of smooth muscle layer were 70 5 1μm2, 6 4 2 6 μm2 and 6 4 2 0 μm2 , There was significant difference compared with model group (all P <0 0 01). Submucosal Fb number was 13.6 ± 4.2 in the model group and 6.8 ± 1.4 in the control group, and the number of lymphocytes and alveolar macrophages was also significantly increased in the model group. NAC group and TGF?