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研究生:柯怡安
研究生(外文):Yi-An Ko
論文名稱:NF-κB-IL-6訊息傳遞路徑在小鼠經呼吸器引發之肺部損傷的角色探討
論文名稱(外文):Role of nuclear factor-κB–interleukin-6 signaling pathway in ventilator-induced lung injury in mice
指導教授:許清玫陳理維陳理維引用關係
指導教授(外文):Ching-Mei HsuLee-Wei Chen
學位類別:碩士
校院名稱:國立中山大學
系所名稱:生物科學系研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2011
畢業學年度:99
語文別:英文
論文頁數:56
中文關鍵詞:巨噬細胞核因子介白素-6發炎反應呼吸器
外文關鍵詞:MacrophageNuclear factorIL-6InflammationVentilator
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呼吸器是一重要的維生工具,然而較長的通氣時間與較高的通氣容積卻會引發肺部的二度傷害,增加感染的機率而造成患者的死亡率上升。介白素-6(IL-6)為一多效性的細胞激素,可調控發炎與抗發炎反應,其在呼吸器所引發之肺部損傷的角色仍有爭議。因此,為了探討呼吸器引發肺部損傷的機轉,以及,將WT、IL6-/-、IL6-/- → WT嵌合小鼠以及IKK△mye小鼠以呼吸器連接六小時後進行分析。此外,藉由給予IL-6抗體進一步了解IL-6在呼吸器所引發肺部損傷中所扮演的角色。實驗結果顯示,呼吸器的通氣刺激會造成肺部微血管通透性及組織嗜中性白血球浸潤程度的增加,而肺部組織與支氣管肺泡沖提液中也有較多的發炎性細胞激素生成。然而給予IL-6抗體的小鼠、IL6-/-、IL6-/- → WT嵌合小鼠以及IKK△mye小鼠皆可減緩肺部發炎以及損傷的情形,因此,介白素-6-核因子-κB訊息傳遞路徑促進的發炎反應與呼吸器引發之肺部損傷有關。此外,呼吸器的通氣刺激會損害肺泡巨噬細胞的抗菌能力,因而增加發展成呼吸器相關肺炎的危險性。
Although mechanical ventilator is a life-saving intervention, longer ventilation time and excessive tidal volume contribute to lung injury and increased incidence of infection which is associated with higher mortality. IL-6, a pleiotropic cytokine, participates in both pro- and anti-inflammatory responses. Till now, opinions of the role of IL-6 are widely divided. To study the pathogenesis mechanism of ventilator-induced lung injury (VILI), C57BL/6 mice (WT), IL-6 knockout mice (IL6-/-), chimera (IL6-/- → WT) and deletion of IκB kinase in the myeloid (IKK△mye) mice were placed on ventilator for 6 hr. WT mice were also given the IL-6-blocking antibody just before ventilation to evaluate the role of IL-6 signaling in VILI. The results revealed that the pulmonary capillary permeability, neutrophil sequestration, macrophage drifting and protein concentration in bronchoalveolar lavage fluid, and the proinflammatory cytokine levels were significantly increased in ventilated WT mice but not in those pretreated with IL-6-blocking antibody as well as IL6-/-, IKK△mye, and IL6-/- → WT chimera mice, suggesting that NF-κB–IL-6 signaling could induce inflammation which contributes to the VILI. Furthermore, the antibacterial ability of alveolar macrophages was impaired by ventilation that subsequently increased the danger of developing to ventilator-associated pneumonia.
Acknowledgement……………………………....…….i
Abstract in Chinese……………………......................ii
Abstract in English…………………...........................iii
Introduction………………............................................1
Materials and Methods…………………………........6
Results…………………………………………....….16
Discussion………………………..............................22
Figures…………………………….............................28
Tables……………………………………………......45
References…………………………….....................47

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