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The Role Of Nuclear Factor-¦ÊB Activation In Traumatic Acute Lung Injury

Posted on:2002-04-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:K L LiaoFull Text:PDF
GTID:1114360032955193Subject:Surgery
Abstract/Summary:PDF Full Text Request
Acute lung injury(ALI) is a common complication after trauma, especially thoracic blunt trauma and may result in acute respiratory distress syndrome(ARDS), systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), or multiple organ failure (MOF) that may contribute to the synthesis of cytokines and other inflammatory mediators. Current study indicates that ALL and ARDS are two stages of one pathologic process, and ARDS may be considered as the terminal stage of ALL, so the therapy of ARDS should emphasize to prevent the development from ALL to ARDS. The pathogenesis of ALl is not clear yet. It is believed that the recruitment and accumulation of neutrophils and macrophages in the lung tissue and the release of proinflammatory mediators are responsible for the lung inflammatory response and lesion after trauma. Nuclear factor-kappa B (NF-kappaB) is a major transcription factor that plays a key role in immune and inflammatory responses by participating in the coordinated expression of most proinflammatory genes. But at present there are few studies about the role of NF-icB activation on the inflammatory responses in the lungs during traumatic ALL. Understanding NF-KB in immune and inflammatory responses may lead to new approaches to treat the ALL after trauma with appropriate inhibitor of NF-kappaB activation in the future. In order to gain an overall understanding of the role of NF-icB on ALL after thoracic blunt trauma, in this study, the model of traumatic ALL in rats and alveolar macrophages stretch-induced injury were established, the NF-w.B .v. activation, hcBa content and the gene expression of TNF-a, IL-S in vivo and vitro were observed with EMSA, Western blotting, RT-PCR, respectively. The changes of NF-icB in ALL due to trauma, endotoximia and trauma combined with endotoximia were compared and the protective effect of pyrrolidine dithiocarbamate (PDTC) on the combined injuiy in rats were observed too. The main results and conclusions are as follows: 1. The models of traumatic ALl with 35OkPa drive pressure on the right lateral superior chest of rats and stretch-induced injury of alveolar macrophges cultured on the silastic membrane plates with 200kPa drive pressure can be established by small multi-functional bio-impact apparatus. The models are suitable to the study of severe chest trauma in vivo or vitro. The severity criterion of lung injury after trauma is proposed 2. The ALL induced by trauma, endotoximia and trauma combined with endotoximia can result in an increase of the pulmonary vascular permeability, content of water in the lung tissue and the accumulation of neutrophils and macrophages, but their pathophysiological processes may be different. There is a additive effect on the severity of injury in lung tissues when two kinds of injuring factors inflict the rats 3. Traumatic ALL induces L1BQ degradation, NF-icB activation and upregulation of TNF-a, IL-8 gene expression in the lungs which are crucial role in ALL pathologic progress. PDTC has protective effect on the rats with combined injury through inhibiting NF-kappaB activation and expression of proinflammatory genes and their products. The significantly different in degree and speed of IicBa degradation, NF-iB activation among the three ALl groups indicate that their mechanisms may be dis...
Keywords/Search Tags:Thoracic Blunt Trauma, Pulmonary Contusion, Acute Lung Injury, Acute Respiratory Distress Syndrome, Systemic Inflammatory Response Syndrome, Nuclear Factor-icB, Tumor Necrosis Factor-a, Interleukin-8, Alveolar Macrophages, Rats
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