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

本项目旨在阐明A型肺实质损伤、I、E、肺气肿和纤维化的发生机制。本课题针对肺实质损伤发生的两种病理假说，即缺氧-抗氧化剂失衡学说和蛋白水解酶-抗酪氨酸酶失衡学说，对博莱霉素(BLM)致肺实质损伤的实验模型进行了研究。实验对象：1)抗氧化剂维生素E(VE)的作用。(2)外源性应用猪胰腺弹性蛋白酶(PPE)的作用。3)香烟烟雾暴露的影响。结果：1)膳食补充VE不能减轻BLM纤维化。2)VE缺氧性肺损伤可引起肺组织病理改变。3)香烟烟雾暴露可改善BLM所致的肺损伤，形成A型肺气肿。4)肌肉注射PPE可减少博莱曼诱导的肝纤维化。讨论：因为A Supp…更多的VE释放并未抑制纤维化的发展，推测过氧化氢是激发A肺纤维化的重要活性氧物种。此外，维生素EDEFICENCY在BLM治疗的早期阶段会导致严重的纤维化改变，但随后会导致肺气肿。由此可见，早期似乎是单线态氧作用并诱导了严重的纤维化改变，而VE可清除的其他活性氧物种如过氧核素、超氧阴离子自由基和超氧阴离子自由基随后发生了明显的改变。香烟烟雾暴露与气管内滴注博莱霉素并存可诱发肺炎性肺损伤。在弹性酶实验中，估计局部远隔器官炎症并存和血清弹性酶活性A水平影响肺实质损伤。高水平的血清弹性蛋白酶活性抑制了中性粒细胞在肺组织中的渗透。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，但在某些调节因素的影响下，两者可能相互进行。较少

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