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    請使用永久網址來引用或連結此文件: https://ir.cnu.edu.tw/handle/310902800/27245


    標題: 探討小鼠急性肺損傷之初期和後期發炎相關分子表現與組織特異性
    Studies on the expression of inflammation-associated moleculars and tissue-specific regulation at an early or later stage in acute lung injury (ALI)-challenged mice.
    作者: 許巧旻
    貢獻者: 保健營養系
    黃惠玲
    關鍵字: 急性肺損傷
    發炎
    高糖化終產物受器
    小鼠
    Acute lung injury
    Inflammation
    Receptor for advanced glycation end products (RAGE)
    mice
    日期: 2013
    上傳時間: 2014-03-11 14:22:40 (UTC+8)
    摘要: 臨床上急性肺損傷 ( Acute lung injury, ALI ) 可能導因於病菌感染、胃酸或異物性吸入,嚴重者會引起急性呼吸窘迫症候群( Acute respiratory distress syndrome, ARDS ) ,造成肺泡微血管被破壞、富含蛋白質的液體滲出造成肺水腫、損害肺部呼吸功能等症狀。在許多ALI動物模式中得知,細胞激素釋放增加,造成小鼠體內抗氧化劑被耗盡,肺血管內皮細胞粘著分子上調和內皮細胞損傷的敏感性增加。本實驗首次利用酸與LPS直接誘發小鼠ALI模式,探討急性肺損傷之初期和後期發炎相關分子表現與組織特異性。採用16週齡之BABL/c雌鼠30隻,經3天適應期後隨機分成2組,其中一組為控制組 (C組),另一組為誘導ALI的實驗組,由氣管滴入0.1 N HCl ( 2 mL/kg BW,0.1 N HCl )及LPS ( 5 mg/kg BW ),於6及24小時犧牲 (6A與24A組) ,每組8-11隻,收集血清、肝臟、肺臟與肺泡沖洗液 ( bronchoalveolar lavage fluid, BALF ),分析其發炎相關指標、氧化/助氧化系統,並測定相關分子之mRNA表現量。ALI效應來看,相對組織重結果,24A組之肺臟顯著重於6A組及C組,6A組及24A組之脾臟及胸腺則顯著重於C組;氧化/助氧化系統方面,24A組之抗氧化分子GSH含量及抗氧化酵素Catalase活性顯著低於C組,GPx活性及myeloperoxidase (MPO) 活性則顯著高於C組,細胞激素方面,血清IL-6、肺臟IL-6以及BALF內IL-6、TNF-α、receptor for advanced glycation end-products (RAGE)、macrophage inflammatory protein-2 (MIP-2)含量在6A組顯著高於24A組及C組,在24A組亦顯著高於C組,肝臟IL-6及TNF-α在C組最高,6A組及24A組間無顯著差異;ALI前期與後期指標變化,比較6小時 (6A組) 與24小時 (24A組) 結果得知,後期-24A組之MPO活性顯著高於前期-6A組,血清IL-6、肺臟IL-6以及BALF之IL-6、TNF-α、RAGE、MIP-2則是前期-6A顯著高於後期-24A。綜合上述,本研究利用氣管滴入酸與LPS,直接刺激誘發小鼠ALI模式,造成肺相對重量與MPO活性隨時間增加而顯著升高,推測肺水腫與發炎細胞浸潤程度可能隨病程時間增加而加劇;IL-6、TNF-α、RAGE、MIP-2等細胞激素,在小鼠ALI初期顯著增加,是病症初期的良好指標。
    Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury (ALI), is associated with an up to 35% mortality rate. Severe sepsis, pneumonia, acid aspiration, and surgical stress are the major causes of ALI/ARDS. In ALI experimental model, ALI is characterized by significant lung oxidative stress and inflammation, which can contribute to cellular injury. Understanding the expression of inflammatory cytokines is an important step in unraveling the pathogenesis of this clinical syndrome. To date, no study had definitively described the effects of different time stages on intratracheal administration acid and LPS induced-ALI in mice. Therefore, the purpose of this study was to determine the expression of inflammation-associated moleculars and tissue-specific regulation at an early or later stage in acute lung injury (ALI)-challenged mice. Mice were randomly assigned to a control group (C), and a ALI group. The control group has none challage. The ALI group were weighed and then anesthetized before inducing ALI by acid and LPS aspiration. Mice received intratracheal instillation of HCl ( 0.1 N; 2 mL/kg BW). After 5 minutes, LPS was instilled intratracheally (10 g in 50 L sterile saline; 5 mg/kg BW). Animals were sacrificed by carbon dioxide asphyxiation at 6 h (6A group) and 24 h (24A group) after acid and LPS challenge. Blood, bronchoalveolar lavage fluid (BALF), lung and liver were collected and assessed for associated parameters, such as inflammatory cytokines, antioxidant defense system. All data are expressed as means ± S.D. The significance of differences between two groups was analyzed by Student’s t-test. The statistical significance level was set at p < 0.05. We found that relative lung weight were significantly increased, the activities of catalase and GSH level in the lung were significantly decreased at 24 hours after ALI challenge (24A group), but the activities of glutathione peroxidase (Se-GPx) were marked increased compared with C group. Interleukin-6 (IL-6) level in serum was significantly increased in both ALI-challenged group. Several inflammatory cytokines, including macrophage inflammatory protein-2 (MIP-2), receptor for advanced glycation end-products (RAGE), IL-6, and tumor necrosis factor alpha (TNF-α) were significantly increased in bronchoalveolar lavage fluid (BALF) after ALI challenge. Similarly, the IL-6 and TNF-α were significantly increased in lung tissue after ALI challage (6A group), but differed from liver. Myeloperoxidase (MPO), a marker of neutrophil infiltration, had a significantly increase during ALI in the lung, and the level in 24A group was higher than those in 6A group. We found that TNF-α, IL-6, MIP-2 and RAGE all were the marked indicators at the early stage after ALI challenge. In conclusion, this study was the first time to elucidate the expression of inflammation-associated moleculars and tissue-specific regulation at an early or later stage in direct ALI-challenged mice. Our results indicated that the RAGE, MIP-2, TNF-α, IL-6 were good markers of the early stage in ALI-challenged mice. The expression of MPO had a tissue-specific manner that the induced level in the lung had a significantly higher than those in the liver after ALI challenge.
    關聯: 電子全文公開日期:20180628,學年度:101,100頁
    顯示於類別:[保健營養系(所) ] 博碩士論文

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