Effects of alpha-lipoic acid on LPS–induced acute lung injury in rat
碩士 === 國防醫學院 === 生理學研究所 === 95 === Acute lung injury(ALI)is a serious and devastating clinical syndrome with high mortality. Clinically, it is characterized by refractory hypoxemia, reduced lung compliance, and the presence of diffuse pulmonary infiltrates on chest radiograph. The predisposing facto...
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ndltd-TW-095NDMC01160052015-10-13T16:41:04Z http://ndltd.ncl.edu.tw/handle/95580320763564703748 Effects of alpha-lipoic acid on LPS–induced acute lung injury in rat 探討硫辛酸對於內毒素誘發急性肺損傷之影響 Ying-Chieh ,Lin 林盈潔 碩士 國防醫學院 生理學研究所 95 Acute lung injury(ALI)is a serious and devastating clinical syndrome with high mortality. Clinically, it is characterized by refractory hypoxemia, reduced lung compliance, and the presence of diffuse pulmonary infiltrates on chest radiograph. The predisposing factors are including pulmonary or non-pulmonary diseases. The current clinical therapeutic strategies for acute lung injury still limited in supportive care and the mortality remains high. Recent evidences suggest that severe oxidative stress is experienced by patients with ALI, and relieving oxidative stress might be ameliorate lung tissue injury. Alpha-lipoic acid(ALA), a dithiol compound, is a crucial prosthetic group of various cellular enzymatic complexes and also serves as a critical role in redox. Recently, ALA has been identified as a potent antioxidant therapeutic agent in the prevention or treatment of diseases with high oxidative stress. The LPS intratracheal instillation (IT) method is a frequent used animal model for studying direct acute lung injury. In the present study, we built up a reliable LPS-induced lung injury murine model.In addition, we evaluated the effects of ALA on this animal model. After IT with LPS(5 mg/kg), and rats were sacrificed at 0, 2, 6,12 and 18 hours after IT. Acute lung injuries were evidenced by increased lung tissue wet/dry ratio and myeloperoxidase(MPO)activity of lung, as well as enhanced PMN counts, protein leakage, and TNF-α,IL-6, IL-1β,MIP-2, CINC-1 levels in bronchoalveolar lavage fluid (BALF) accompanied by pathological changes. Animals received pretreatment with ALA one hour prior LPS IT instillation and sacrificed at 6 hours later. ALA significant alleviated lung injury severity. In further, the proinflammatroy cytokines (TNF-α, IL-1β and IL-6), MIP-2, systemic ROS were significantly suppressed. Meanwhile, ALA inhibited LPS-induced inducible nitric oxide synthase (iNOS) gene expression but upregulated of heme oxygenase-1 (HO-1) gene expression in lung tissue. In conclusion, we demonstrated that ALA has beneficial effect in LPS-induced ALI by inhibition of pro-inflammatory cytokines, chemokines, ROS formation and iNOS expression, but enhancement of HO-1 expression. Tz-Chong ,Chou 周志中 2007 學位論文 ; thesis 93 zh-TW |
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碩士 === 國防醫學院 === 生理學研究所 === 95 === Acute lung injury(ALI)is a serious and devastating clinical syndrome with high mortality. Clinically, it is characterized by refractory hypoxemia, reduced lung compliance, and the presence of diffuse pulmonary infiltrates on chest radiograph. The predisposing factors are including pulmonary or non-pulmonary diseases. The current clinical therapeutic strategies for acute lung injury still limited in supportive care and the mortality remains high. Recent evidences suggest that severe oxidative stress is experienced by patients with ALI, and relieving oxidative stress might be ameliorate lung tissue injury. Alpha-lipoic acid(ALA), a dithiol compound, is a crucial prosthetic group of various cellular enzymatic complexes and also serves as a critical role in redox. Recently, ALA has been identified as a potent antioxidant therapeutic agent in the prevention or treatment of diseases with high oxidative stress. The LPS intratracheal instillation (IT) method is a frequent used animal model for studying direct acute lung injury. In the present study, we built up a reliable LPS-induced lung injury murine model.In addition, we evaluated the effects of ALA on this animal model. After IT with LPS(5 mg/kg), and rats were sacrificed at 0, 2, 6,12 and 18 hours after IT. Acute lung injuries were evidenced by increased lung tissue wet/dry ratio and myeloperoxidase(MPO)activity of lung, as well as enhanced PMN counts, protein leakage, and TNF-α,IL-6, IL-1β,MIP-2, CINC-1 levels in bronchoalveolar lavage fluid (BALF) accompanied by pathological changes. Animals received pretreatment with ALA one hour prior LPS IT instillation and sacrificed at 6 hours later. ALA significant alleviated lung injury severity. In further, the proinflammatroy cytokines (TNF-α, IL-1β and IL-6), MIP-2, systemic ROS were significantly suppressed. Meanwhile, ALA inhibited LPS-induced inducible nitric oxide synthase (iNOS) gene expression but upregulated of heme oxygenase-1 (HO-1) gene expression in lung tissue. In conclusion, we demonstrated that ALA has beneficial effect in LPS-induced ALI by inhibition of pro-inflammatory cytokines, chemokines, ROS formation and iNOS expression, but enhancement of HO-1 expression.
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author2 |
Tz-Chong ,Chou |
author_facet |
Tz-Chong ,Chou Ying-Chieh ,Lin 林盈潔 |
author |
Ying-Chieh ,Lin 林盈潔 |
spellingShingle |
Ying-Chieh ,Lin 林盈潔 Effects of alpha-lipoic acid on LPS–induced acute lung injury in rat |
author_sort |
Ying-Chieh ,Lin |
title |
Effects of alpha-lipoic acid on LPS–induced acute lung injury in rat |
title_short |
Effects of alpha-lipoic acid on LPS–induced acute lung injury in rat |
title_full |
Effects of alpha-lipoic acid on LPS–induced acute lung injury in rat |
title_fullStr |
Effects of alpha-lipoic acid on LPS–induced acute lung injury in rat |
title_full_unstemmed |
Effects of alpha-lipoic acid on LPS–induced acute lung injury in rat |
title_sort |
effects of alpha-lipoic acid on lps–induced acute lung injury in rat |
publishDate |
2007 |
url |
http://ndltd.ncl.edu.tw/handle/95580320763564703748 |
work_keys_str_mv |
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