白细胞介素12在大鼠肺缺血再灌注损伤中的作用

Role of IL-12 in lung ischemia-reperfusion injury in rats

目的评价白细胞介素12（IL-12）在大鼠肺缺血再灌注损伤中的作用。方法健康成年雄性SD大鼠24只，8～10周龄，体重250～280g，采用随机数字表法，将大鼠随机分为3组（n=8）：假手术组（s组），肺缺血再灌注损伤组（I／R组），IL-12单克隆抗体组（IL-12组）。S组只分离肺门不夹闭；I／R组夹闭肺门60min后，恢复灌注2h；IL-12组于夹闭肺门前1h尾静脉注射IL-12单克隆抗体200μg／kg。于再灌注结束时采集血样和肺组织，测定血浆TNF—α浓度、辅助性T细胞（Th）1和Th2水平、肺组织湿干重（W／D）比、髓过氧化物酶（MPO）活性、MDA含量及动脉血氧分压（PaO2）及二氧化碳分压（PaCO）。光镜下观察肺组织病理学改变。结果与s组比较，I／R组和IL-12组肺组织W／D比、MDA含量、MPO活性、血浆TNF-α浓度升高，I／R组PaO2降低，PaCO2、Th1水平和Th1／Th2升高（P〈0．01），Th2水平差异无统计学意义（P〉0．05），IL-12组PaO2、PaCO2、Th1、Th2水平及Th1／Th2差异无统计学意义（P〉0．05）；与I／R组比较，IL-12组PaCO2、肺组织W／D比、MDA含量、MPO活性、血浆TNF-Ⅱ浓度、Th1水平和Th1／Th2降低，Th2水平和PaO2升高（P〈0．01）。I／R组肺组织损伤明显，IL-12组肺组织损伤程度明显减轻。结论IL-12通过使Th1／Th2失衡而参与肺缺血再灌注损伤。

Objective To investigate the role of IL-12 in lung ischemia-reperfusion （I/R） injury in rats. Methods Twenty-four healthy male SD rats, 8-10 weeks, weighing 250-280 g, were randomly divided into 3 groups （n = 8 each）： sham operation group （S）, I/R group, IL-12 monoclonal antibody group （group IL-12）. Lung I/R was induced by clamping the left hilum of lung for 60 min followed by 120 rain reperfusion in groups I/R and IL-12. IL-12 monoclonal antibody 200 μg/kg was injected via the eaudal vein at 1 h before clamping the left hilum. The blood samples were collected at the end of reperfusion, the rats were then sacrificed and lungs removed for determination of the plasma TNF-α concentration, Thl and Th2 levels, W/D lung weight ratio, MDA content, MPO activity, PaOz and PaCO2 in lung tissues and for microscopic examination. Results Compared with group S, W/D ratio and the level of MPO, MDA and TNF-α were significantly increased in groups I/R and IL-12, and PaO2 was significantly decreased, and PaCO2, Thl level and Th1/Th2 were significantly increased in group I/R （P 〈 0.01）, and no significant change was found in PaO2 , PaCO2 , the level of Th1 and Th2, and Th1/Th2 in group IL-12 （ P 〉 0.05）. PaCO2 ,W/D ratio, the levels of MDA, MPO, plasma TNF-α, Th1 and Thl/Th2 were significantly lower, and Th2 level and PaCO2 were significantly higher in group IL-12 than in group I/R （ P 〈 0.01 ）. The pathologic changes of the lung were attenuated in group IL-12. Conclusion IL-12 is involved in the lung I/R injury through inducing Thl/Th2 imbalance in rats.