Study on endotoxin-induced acute lung injury and antagonizing effects of naproxen in rabbits

Objective: To study the pathogenesis of endotoxin（ET）-induced acute lung injury（ALI） and the antagonizing effects of naproxen in rabbits. Methods: 24 Flap-eared white rabbits were randomly assigned to three groups: control group（group A）, ET-treated group（group B） and combination group（treated by ET and naproxen, group C）. ALI was induced by intravenous injection of ET（600 μg/kg） by jugular vein. During the experiment, arterial blood gases, the contents of TXB₂ and 6-keto-PGF_1α in both serum and lung tissue were measured. When rabbits were killed at 4h of the experiment, the pathologic changes of pulmonary tissue were examined with light microscope, and Peroxisome proliferator-activated receptor γ（PPARγ） were examined by immunohistochemistry. Results: Compared with group A, rabbits of group B showed PaO₂ decreased, the contents of TXB₂ and 6-keto-PGF_1α increased in both serum and lung tissue （P＜0.01）; the pathological examination showed obviously injury in pulmonary tissue;the contents of TXB₂ and 6-keto-PGF_1α in serum and lung tissue were lower in group C than those in group B. Pulmonary edema and inflammatory cell infiltration were obviously severe in group B compared with those seen in group C. The expression of pulmonary PPARγ in group C was better than that in group B. Conclusion: An intravenous injection of ET can reproduce ALI model in rabbits.Cylcooxygenase（COX） was activated during the period of ALI and it was an important factor in pathogenesis of ET-induced ALI. The decreased PPARγ expression was found in ET-induced ALI.Naproxen had some protective effects to ET-induced ALI in rabbits by means of activating PPARγ and antagonizing COX activities.