Role of Neutrophil elastase on ventilation-induced lung injury
碩士 === 長庚大學 === 臨床醫學研究所 === 103 === Background：Mechanical ventilation（MV）is commonly used as a life-supportive strategy for patients with acute respiratory distress syndrome（ARDS）. High-tidal-volume MV in health animals has been used to simulate the overdistension of the less injury and thus more-co...
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2014
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| Online Access: | http://ndltd.ncl.edu.tw/handle/73175183826592319057 |
| Summary: | 碩士 === 長庚大學 === 臨床醫學研究所 === 103 === Background：Mechanical ventilation（MV）is commonly used as a life-supportive strategy for patients with acute respiratory distress syndrome（ARDS）. High-tidal-volume MV in health animals has been used to simulate the overdistension of the less injury and thus more-compliant areas of lung found in ARDS﹒Ventilator-induced lung injury（VILI）is characterized by the disruption of endothelial and epithelial barriers through production of the inflammatory cytokines，reactive oxygen species，and neutrophil influx﹒Neutrophil elastase、nuclear factor-κB（NF-κB）、NF-κB repressing factor（NRF）have previously been demonstrated to participate in modulation of macrophage inflammatory protein-2（MIP-2） during ARDS﹒However，the mechanisms regulating interaction among MV，neutrophil sequestration，and NF-κB and NRF are unclear﹒Therefore，we hypothesized that neutrophil elastase inhibitor reduced MV-induced neutrophil infiltration and MIP-2 production via inhibition of NF-κB and NRF signaling pathway﹒
Methods：C57BL/6 mice，aged between 6 and 8 weeks，weighting between 20 and 25g，were exposed to low-tidal-volume（6ml/kg）or high-tidal volume（30ml/kg）MV using room air with or without pharmacological inhibition with 2mg/kg NF-κB inhibitor SN-50 or 6mg/kg NRF short interfering RNA（siRNA）or 100mg/kg neutrophil elastase inhibitor﹒Nonventilated mice were used as a control group﹒
Results：Neutrophil elastase inhibitor attenuated high-tidal-volume ventilation induced lung injury，production oh MIP-2 and malondialdehyde，neutrophil recruitment，activation of NF-κB and NRF，apoptotic epithelial cell death and damage of brochial microstructure in mice﹒Mechanical stretch-augmented acute lung injury was also abolished through pharmacological inhibition of NF-κB activation by SN-50 and NRF expression by NRF siRNA﹒
Conclusion：These data suggest that neutrophil elastase inhibitor reduces high-tidal-volume MV-promoted neutrophil accumulation，oxidative stress，and MIP-2 production via inhibition of NF-κB and NRF signaling pathway﹒
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