DEVELOPMENTAL MECHANISMS OF LUNG PARENCHYMAL INJURY EMPHYSEMA AND FIBROSI - CELL TO CELL INTERACTION IN LUNG PARENCHYMA -

本项目旨在阐明肺实质损伤，如肺气肿和纤维化的发生机制。为了开展本课题，我们针对肺实质损伤发生的两种病理假设，即抗氧化-抗氧化失衡理论和蛋白酶-抗蛋白酶失衡理论。我们建立了气管内给药博来霉素（blm）致肺实质损伤的实验模型。实验对象：1)抗氧化剂维生素e （ve）的作用。2)外源性猪胰腺弹性酶（ppe）的作用。3)香烟烟雾暴露的影响。结果：1)膳食补充ve没有减轻BLM纤维化。2)在blm致肺损伤中，ve缺乏导致肺气肿改变。3)香烟烟雾暴露可改变blm诱导的肺损伤产生肺气肿。4)肌内注射ppe可减少BLM诱导的纤维化。讨论：由于添加更多的VE元素并不能抑制纤维化的发展，推测过氧化氢是一种重要的活性氧，可以促进肺纤维化。否则，在BLM治疗的早期，维生素缺乏会引起严重的纤维化改变，但最终会诱发肺气肿。从这些结果来看，单线态氧似乎在早期作用并诱导了严重的纤维化变化，而其他活性氧如过氧化物自由基、氢过氧化物自由基和超氧阴离子自由基可以被ve清除，随后发生肺气肿变化。香烟烟雾暴露与BLM气管内灌注共存可导致肺气肿性肺损伤。在弹性酶实验中，估计局部远端器官炎症和血清弹性酶活性水平共存影响肺实质损伤。高水平的血清弹性酶活性抑制了肺组织中中性粒细胞的浸润。这些结果表明，尽管肺纤维化和肺气肿被认为是最终的、不同形式的实质损伤，但在一些调节因素的影响下，两者可能相互过渡。少

THIS PROJECT AIMED TO CLARIFY THE MECHANISMS TO PRODUCE A LUNG PARENCHYMAL INJURY, I,E, EMPHYSEMA AND FIBROSIS. TO PROCEED THIS PROJECT,WE HAVE ORIENTED TO TWO PATHOLOGICAL HYPOTHESES ON THE DEVELOPMENT OF LUNG PARENCHYMAL INJURY,ANOXIDANT-ANTIOXIDANT IMBALANCE THEORY AND A PROTEASE-ANTIPROTEASE IMBALANCE THEORY.WE HAVE BEEN STUDIED FOLLOWING SUBJECTS ON EXPERIMENTAL MODELS OF LUNG PARENCHYMAL INJURY INDUCED BY INTRATRACHEALLY ADMINISTERED BLEOMYCIN (BLM). SUBJECTS OF EXPERIMENT: 1) EFFECT OF ANTIOXIDANT AGENT VITAMIN E (VE). 2) EFFECT OF EXOGENOUSLY ADMINISTERED PORCINE PANCREATIC ELASTASE (PPE). 3) EFFECT OF CIGARETTE SMOKE EXPOSURE. RESULTS: 1) DIETARY SUPPLEMENT OF VE DID NOT REDUCE BLM FIBROSIS. 2) VE DEFFICIENCY CONSEQUENTLY INDUCED THE EMPHYSEMATOUS CHANGE IN BLM-ADMINISTERED LUNG INJURY. 3) CIGARETTE SMOKE EXPOSURE MODIFIED BLM-INDUCED LUNG INJURY TO PRODUCE A EMPHYSEMA. 4) INTRAMUSCULARLY ADMINISTERED PPE REDUCED AN INDUCTION OF BLM INDUCED FIBROSIS. DISCUSSION: BECAUSE A SUPP … More LEMENTATION OF VE DID NOT INHIBIT THE DEVELOPMENT OF FIBROSIS,IT IS SPECULATED HYDROGEN PEROXIDE IS AN IMPORTANT ACTIVE OXYGEN SPECIES TO INCITE A LUNG FIBROSIS. OTHERWISE VITAMIN EDEFICIENCY CAUSED A SEVERE FIBROTIC CHANGE IN EARLY STAGE OF BLM TREATMENT, BUT CONSEQUENTLY INDUCED AN EMPHYSEMA. FROM THESE RESULTS, IT SEEMED A SINGLET OXYGEN ACTED AND INDUCED A SEVERE FIBROTIC CHANGE IN THE EARLY STAGE AND OTHER ACTIVE OXYGEN SPECIES SUCH AS PEROXIRADICAL, HYDROPEROXIRADICAL AND SUPEROXIDE ANION RADICAL WHICH COULD BE SCAVENGED BY VE FOLLOWED AN EMPHYSEMATOUS CHANGE. COEXIST OF CIGARETTE SMOKE EXPOSURE AND INTRATRACHEAL INSTILLATION OF BLM INFERED TO DEVELOPE AN EMPHYSEMATOUS LUNG INJURY. IN ELASTASE EXPERIMENT, IT IS ESTIMATED COEXIST OF LOCAL DISTANT ORGAN INFLAMMATION AND A LEVEL OF SERUM ELASTASE ACTIVITY AFFECT THE LUNG PARENCHYMAL INJURY. A HIGH LEVEL OF SERUM ELASTASE ACTIVITY RESTRAINED NEUTROPHIL INFILTRATION IN THE LUNG TISSUE. THESE RESULTS SUGGEST THAT ALTHOUGH PULMONARY FIBROSIS AND EMPHYSEMA HAVE BEEN CONSIDERED TO BE FINAL AND DIFFERENT FORMS OF PARENCHYMAL INJURY, EACH MAY PROCEED TO THE OTHER UNDER THE INFLUENCE OF SOME MODULATING FACTORS. Less