实验性肺气肿、肺动脉高压发病机理及中药814防治的进一步研究
摘要
慢性阻塞性肺疾病(Chronic Obstructive Pulmonary Disease，COPD)是以慢性进行性的气道阻塞为特征的一组肺部疾病的总称，主要包括慢性支气管炎和肺气肿等。COPD病因学以及防治研究有许多进展，但仍有很多机理不清楚，而且无理想防治措施。迄今，大多数研究认为肺内蛋白酶失衡、感染和烟雾引起的气道炎症、肺内免疫反应异常以及氧自由基增多等因素是诱发、维持肺基质损伤，促进COPD发生和发展的重要环节。此外，近些年研究发现，肺表面活性物质及其组分在维持气道稳定性、调节肺内免疫和炎症反应中有重要的作用，内源性表面活性物质的功能和合成分泌障碍参与了COPD的发生，因此改善和恢复肺内表面活性物质的功能有助于COPD患者症状的缓解，提高治疗效果。
中药814是近几年医科院血研所从活血化瘀中草药中研制的一种新药，前期研究表明具有明显的抗缺氧、降低肺动脉高压、改善心肺循环、抗炎、抑菌以及增强细胞免疫等功能，但尚未用于防治肺气肿。本研究通过建立肺气肿、肺动脉高压地鼠混合模型，观察814对肺动脉压、肺组织结构、血清NO、肺间质(胶原、纤维粘连蛋白等)以及肺表面活性物质(磷脂和相关蛋白)的影响，进一步探讨814对肺气肿、肺动脉高压的防治效果和可能的作用机制；同时探讨内源性表面活性物质在肺气肿发病中的作用。另外，通过体外培养肺泡巨噬细胞、L929细胞和肺泡Ⅱ型上皮细胞，观察814在肺泡巨噬细胞释放某些炎症因子和凋亡诱导中的作用，以及对肺泡Ⅱ型上皮细胞表面活性物质基因表达的影响，以探讨814防治肺气肿、肺动脉高压可能的作用环节。本研究主要包括以下五方面的实验工作：
1．金黄地鼠肺气肿+肺动脉高压模型的建立以及中药814的防治观察：采用气道一次性注入弹性蛋白酶，一月后常压缺氧15天[(10±1)％]，建立肺气肿、肺
Chronic obstructive pulmonary diseases (COPD) is a series of chronic and progressive airway diseases, including emphysema and chronic bronchitis etc. Many advances were achieved in research of pathogenesis, prevention and therapy of COPD, but pathogenesis of COPD has not been completely understood and there are not ideal approaches to prevent and treat it either. So far the majority of researches considered that imbalance of proteinase/antiproteinase system, airway inflammation, immune abnormality and oxidative damage were responsible for inducing, maintaining degradation of lung parenchyma and promoting development or progress of COPD. Recent year's study proved that pulmonary surfactant played a major role in maintaining airway stability, immunomodulation and barrier function etc. Dysfunction in composition and function of pulmonary surfactant in COPD might be one of the mechanisms leading to increasing airway resistance and be concerned with development of COPD. Therefore, improvement of endogenous surfactant is helpful in relieving symptom of COPD and meliorating effect of therapy.
Chinese herbs 814 is a new drug developed by Blood Diseases Institute of Chinese Medical Scientific Academy. Previous researches showed that it was able to obviously decrease pulmonary hypertension, improve circulation of heart and brain, inhibit bacteria, anti-inflammation and reinforce cell-mediated immunity etc. On one hand, our researches established Syrian golden hamsters model of emphysema and pulmonary hypertension to observe the effect of herbs 814 on pulmonary artery pressure, pulmonary tissue structure, NO in serum, pulmonary extracellular matrix (collagen and fibronectin) and pulmonary surfactant (phospholipids and proteins). On
中药814是近几年医科院血研所从活血化瘀中草药中研制的一种新药，前期研究表明具有明显的抗缺氧、降低肺动脉高压、改善心肺循环、抗炎、抑菌以及增强细胞免疫等功能，但尚未用于防治肺气肿。本研究通过建立肺气肿、肺动脉高压地鼠混合模型，观察814对肺动脉压、肺组织结构、血清NO、肺间质(胶原、纤维粘连蛋白等)以及肺表面活性物质(磷脂和相关蛋白)的影响，进一步探讨814对肺气肿、肺动脉高压的防治效果和可能的作用机制；同时探讨内源性表面活性物质在肺气肿发病中的作用。另外，通过体外培养肺泡巨噬细胞、L929细胞和肺泡Ⅱ型上皮细胞，观察814在肺泡巨噬细胞释放某些炎症因子和凋亡诱导中的作用，以及对肺泡Ⅱ型上皮细胞表面活性物质基因表达的影响，以探讨814防治肺气肿、肺动脉高压可能的作用环节。本研究主要包括以下五方面的实验工作：
1．金黄地鼠肺气肿+肺动脉高压模型的建立以及中药814的防治观察：采用气道一次性注入弹性蛋白酶，一月后常压缺氧15天[(10±1)％]，建立肺气肿、肺
Chronic obstructive pulmonary diseases (COPD) is a series of chronic and progressive airway diseases, including emphysema and chronic bronchitis etc. Many advances were achieved in research of pathogenesis, prevention and therapy of COPD, but pathogenesis of COPD has not been completely understood and there are not ideal approaches to prevent and treat it either. So far the majority of researches considered that imbalance of proteinase/antiproteinase system, airway inflammation, immune abnormality and oxidative damage were responsible for inducing, maintaining degradation of lung parenchyma and promoting development or progress of COPD. Recent year's study proved that pulmonary surfactant played a major role in maintaining airway stability, immunomodulation and barrier function etc. Dysfunction in composition and function of pulmonary surfactant in COPD might be one of the mechanisms leading to increasing airway resistance and be concerned with development of COPD. Therefore, improvement of endogenous surfactant is helpful in relieving symptom of COPD and meliorating effect of therapy.
Chinese herbs 814 is a new drug developed by Blood Diseases Institute of Chinese Medical Scientific Academy. Previous researches showed that it was able to obviously decrease pulmonary hypertension, improve circulation of heart and brain, inhibit bacteria, anti-inflammation and reinforce cell-mediated immunity etc. On one hand, our researches established Syrian golden hamsters model of emphysema and pulmonary hypertension to observe the effect of herbs 814 on pulmonary artery pressure, pulmonary tissue structure, NO in serum, pulmonary extracellular matrix (collagen and fibronectin) and pulmonary surfactant (phospholipids and proteins). On
引文
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