内毒素致家兔急性肺损伤及萘普生保护性作用的研究

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

目的:探讨大肠杆菌内毒素(ET)致兔急性肺损伤(ALI)的发病机制及萘普生的干预作用。方法:24只大耳白兔随机均分为对照组(A组)、ET致伤组(B组)、ET致伤+萘普生处理组(C组)。颈静脉注射ET(600μg/kg)致兔ALI,监测动物动脉血气、血清和肺组织中TXB2和6-keto-PGF1α含量的变化。于4h处死动物,取肺组织观察病理变化及用免疫组化方法检查过氧化物酶增殖子活化受体γ(PPARγ)的表达情况。结果:与对照组相比,损伤组动物动脉血氧分压(PaO2)下降、血清及肺组织中TXB2和6-keto-PGF1α含量增加(P<0.01);肺组织出现明显的病理损害。萘普生处理组PaO2未见明显下降,血清及肺组织中TXB2和6-keto-PG1α值低于ET组;病理检查见轻度肺水肿,炎细胞浸润较ET组少。免疫组化见损伤组肺组织PPARγ表达明显下降,萘普生组好于损伤组。结论:静脉注射ET可复制兔ALI动物模型;环氧合酶(COX)在ALI时激活,PPARγ表达减少。萘普生可能通过抑制COX的活性和激活PPARγ对ALI有一定的干预作用。

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-PGFloin 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 Peroxiseme 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-PGF1α 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-PGF1α 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 ALL 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.