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The Change Of Cytokines And Nuclear Factor-kappa B In Lung Tissue Of LPS-induced Acute Lung Injury In Neonatal Rats: The Effect Of N-acetylcysteine

Posted on:2005-06-26Degree:DoctorType:Dissertation
Country:ChinaCandidate:J JinFull Text:PDF
GTID:1104360122490958Subject:Academy of Pediatrics
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The pathological characteristic of acute lung injury ( ALI) is diffused alveolar-capillary membrane injury, which were caused by severe infection , trauma, shock , et al. The severe stage is acute respiratory distress syndrome (ARDS). The pathogenesis is still not clear although many studies have been done. Recently the attention was paid to inflammatory response , and it is regarded that All is the result of uncontrolled inflammatory response in the lung due to various causes . It is the pulmonary manifestation of systemic inflammatory response.The study about ALI/ARDS in neonate is delayed because many diseases in neonatal period , such as RDS, pneumoniae, aspiration syndrome, persistent pulmonary hypertension, pulmonary hemorrhage et al, haye the similar clinical manifestations and X - ray findings to ARDS, making it difficult to distinguish them. Until 1989 Faix et al. reported 11 cases of ARDS in full - term neonate. After that report, there were many reports of ARDS in neonate. ALI in neonate has a lot of differences compared with in adults and children. ALI in neonate should not be ignored.Iipopolysacchrides ( LPS) is a major constituent of endotoxin of gram -negtive becteria. It is often be used to produce animal model of AO in adult rats. Less studies have been done on LPS - induced All in neonatal rats. Infection is one of common reasons causing ALI in neonate. In this study , LPS wasused to produce ALI in neonatal rats according previous studies.Timella et al. made a alveolitis model in neonatal rats but not lung injury, using IPS of 0. 03mg/kg. And using 5mg/kg LPS can cause pulmonary hemorrhage. Clinically it is not common that ALI in neonate manifested pulmonary hemorrhage. According to Demirakca's report , ALI/ARDS in neonate did not all manifest pulmonary hemorrhage and pulmonary hemorrhage is not all caused by ALI/ARDS. Pulmonary hemorrhage is not quite fit for the fact of ALI/ARDS in neonate. In this study, 1 ~ 4 mg/kg of LPS were injected intraperitoneally , to find a dose to make ALI in neonatal rats but not pulmonary hemorrhage. The changes of cytokines and nuclear factor - kappa B were studied in lung tissue of LPS - induced ALI/ARDS in neonatal rats, in order to have a more clear look of pathogenesis of ALI/ARDS in neonate.The studies of cytokines and its regulation are important in ALI pathogenesis . It is very important for revealing the molecular mechanism of ALI and for the targeted treatment about cytokines. The characteristic of ALI is the uncontrolled inflammatory response. The high risk factors of AU/ARDS can active the target cell, causing cascade inflammatory response, and resulting in systemic inflammatory response syndrome (SIRS). While in parallel to the inflammatory response , the body mounts a compensatory anti - inflamamtory response syndrome (CARS) in order to counter inflammatory mediators . If SIRS and CARS are dynamically balanced, homeostasis can be restored. So how to enhance CARS and inhibit SIRS in order to restore the balance of inflammation and how to interrupt the inflammatory cascade reaction have become the focus study on ALI/ARDS.As an important proinflammatory cytokine , TNF-a has strong damage effect to lung tissue. It can cause lung injury through various mechanisms. IL -18 is a strong stimulatory factor for cellular immune. When inflammation ,it can cause tissue injury; while it still has anti - microbes and anti - tumor effects. IL - 18 may play a " double - sword" role in ALI. There is no finding about role of IL - 18 in LPS - induced ALI. If overexpressed IL - 18 induce ALI is still not known. In inflammation, mononuclear and macrophage secret some kinds of proinflammatory cytokines, then produce IL - 10. As an important humoral im-munol factor , IL -10 inhibits secretion of proinflammatory cytokines to balance the immunity response , therefore IL -10 plays a protective role.NF - kB involves in transcriptional regulation of many cytokines and inflammatory mediators'genes. Also it plays an important role in regulation of cy...
Keywords/Search Tags:neonate, acute lung injury (ALI), lipopolysacchride(LPS), rat, maleic dialdehyde(MDA), superoxide dismutase(SOD), glutathione per-oxidase(GSH-PX), immunohistochemistry, reverse transcription polymerase chain reaction ( RT - PCR)
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