Effect of FC-77 on Ischemia-Reperfusion - Induced Acute Lung Injury

• Main Authors: Reui Ying Li, 李瑞瑩
• Other Authors: Min-Hui Li
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/64210768269488162095

碩士 === 國防醫學院 === 航太醫學研究所 === 97 === Abstract Background: In recent years, the lung transplantation has marked advances. But 10 – 20 % patients with lung transplantation have severe lung dysfunction due to ischemia-reperfusion injury. Evidence indicates that ischemia and hypoxia process in the lung will induce proinflammatory cytokine production, which will not only enhance vascular endothelial permeability but also activate neutrophils. Many studies have shown that ischemia-reperfusion on brain, liver and kidney causes transcription factor AP-1and NF-κB activation. Both transcription factors consequently promote a variety of cytokine production, resulting in an inflammatory cascade. In recent, the study demonstrates that the intravenous fluorinet (FC-77) attenuated phorbol myristate acetate-induced acute lung injury. The protective mechanism was due to, at least in part, inhibit inflammatory cytokine production. However, the effect of FC-77 on ischemia-reperfusion induced acute lung injury was not investigated. In this study, we will investigate whether FC-77 has protective effect in I-R induced lung injury. The role of transcription factor AP-1 in I-R is also studied. Method: We used an isolated and perfused rat lung model. Lung was subject to 60 min ischemia and 60 min reperfusion to cause acute lung injury. Rats were divided into 7 groups; control group: rat lung was perfused for 120 min without I-R; I-R group: rat lung had I-R; FC-77 group: pretreatment with different dose of FC-77 ( 0.01%, 0.05%, 0.1%, 0.5% ) before I-R. The parameters for evaluation of lung injury include pulmonary artery pressure change (PAP), lung weight gain (LWG), lung weight and body weight ratio (LW/BW), wet and dry lung weight ratio (W/D ratio), capillary filtration coefficient (Kfc), protein concentration of bronchoalveolar fluid (BALF) and lung pathology. In addition, the number of neutrophil, MDA concentration, MPO level, and AP-1 activity in lung tissue, TNF-α and CNC-1 concentrations in perfusate were measured. Results: I/R-induced acute lung injury caused pulmonary hypertension, and significantly increased the LWG, Kfc, LW/BW, and W/D ratio, as well as the protein content in BALF (P<0.05). AP-1 level, MDA concentration and MPO activity in lung tissue, and TNF-α and CNC-1 concentrations in perfusate were significantly increased. In the lung pathology, increased neutrophil infiltration and interstitial edema were found. Pretreatment with the FC-77 in a dose-dependent manner attenuated the increase in these parameters (P < 0.05). Conclusion: In our study, FC-77 dose-dependently attenuated acute lung injury induced by I-R. The protective mechanism may be due to inhibit proinflammatory cytokine production, decrease lipid peroxidation, and suppress AP-1 activation.