后处理对缺血再灌注损伤大鼠肺Egr-1和IL-1β表达的影响

Effect of ischemic post-conditioning on Egr-1 and IL-1β expression in ischemia-reperfusion injured lung in rats

目的:研究后处理对在体缺血再灌注损伤大鼠肺早期生长反应因子1(Egr-1)和白细胞介素1β(IL-1β)表达的影响,并分析其可能的肺保护作用机制。方法:建立大鼠在体肺脏缺血再灌注损伤模型,将SD大鼠24只随机分为假手术(sham)组、缺血再灌注(I/R)组和缺血后处理(IPostC)组,每组8只。在体鼠I/R损伤模型制备完成后,阻断左肺门,终止血供及通气,造成左肺缺血,达预定时间后松开阻断带恢复血供及通气形成再灌注损伤。sham组只游离左侧肺门、套阻断带但不阻断,等待3 h后直接取标本;I/R组缺血1 h后再灌注2 h;IPostC组缺血1 h后给予重复3次的5 min灌注和5 min缺血的后处理,继以恢复血供行再灌注1.5 h。3组实验结束后均留取左侧肺组织,制成10%的组织匀浆,用于测定髓过氧化物酶(MPO)的含量;留取小块肺组织测定肺湿/干重比(W/D),并在光镜下观察肺组织的病理变化;RT-PCR法检测Egr-1 mRNA及IL-1βmRNA的表达量。结果:3组间各项检测指标比较,差异均显著(P<0.05)。与sham组比较,I/R组肺组织中Egr-1 mRNA、IL-1βmRNA的表达量、MPO的活性及W/D值均明显升高(P<0.05);肺组织炎症反应明显加重。IPostC组肺组织中Egr-1 mR-NA及IL-1βmRNA的表达量、MPO的活性及W/D值与I/R组相比均明显下降(P<0.05);肺组织炎症反应明显减轻。结论:后处理能够明显减轻大鼠肺缺血再灌注损伤,其机制可能与抑制Egr-1和IL-1β的表达有关。

AIM：To investigate the protective effects of ischemic post-conditioning on the expression of early growth response factor 1（Egr-1） and interleukin-1β（IL-1β） in ischemia-reperfusion injured lung in rats.METHODS：The model of lung ischemia-reperfusion injury was established in 24 rats and the rats were randomly allocated to 3 different groups（n=8 in each group）：（1） sham group：only sham operation（thoracotomy） and no ischemia for 3 h;（2）ischemia-reperfusion group（I/R group）：interruption of pulmonary perfusion and ventilation for 1 h followed by reperfusion for 2 h;（3） ischemic post-conditioning group（IPostC group）：ischemic post-conditioning（5 min of reperfusion and 5 min of ischemia for 3 times） between the end of ischemia and the beginning of the reperfusion followed by reperfusion for 1.5 h.The lung tissues（prepared to small pieces of about 20 mg） were collected and homogenized at the end of the experiment.The concentration of myeloperoxidase（MPO） in the homogenate was determined.The wet to dry weight ratio（W/D） of the lung tissues was also measured at the end of reperfusion.The pathological changes of the lung tissues were observed under light microscope after reperfusion.The mRNA expression of Egr-1 and IL-1β in the lung tissues was detected by RT-PCR.RESULTS：Compared with sham group,the mRNA expression of Egr-1 and IL-1β,the levels of MPO and W/D were significantly increased in I/R group（P〈0.05）.The inflammatory responses of the lungs in I/R group were significantly severer than those in sham group.Compared with I/R group,the mRNA expression of Egr-1 and IL-1β,the levels of MPO and W/D in IPostC group were significantly decreased（P〈0.05）.The inflammatory responses of the lungs in IPostC group were also significantly attenuated.CONCLUSION：Ischemic post-conditioning significantly reduces ischemic reperfusion injury of the lung by inhibiting the expression of Egr-1 and IL-1β.