缺血后处理抑制大鼠肠缺血再灌注后肺组织核因子-κB活化及ICAM-1的表达

Ischemic postconditioning inhibits activation of nuclear factor-κB and ICAM-1 expression in lungs following intestinal ischemia reperfusion in rats

目的:研究缺血后处理(Ⅰ-postC)对大鼠肠缺血/再灌注(Ⅱ/R)后肺组织核因子-κB(NF-κB)及细胞间黏附分子-1(ICAM-1)表达的影响,探讨Ⅰ-postC对Ⅱ/R后肺的保护作用及机制。方法:32只健康雄性Wistar大鼠随机分为假手术(sham)组、Ⅱ/R组、肠缺血后处理(Ⅱ-postC)组和肢体缺血后处理(LⅠ-postC)组,以无创动脉夹夹闭肠系膜上动脉45 min,再灌注2 h建立小肠I/R模型,采集动脉血进行血气分析,测定肺系数判定组织水肿情况,光镜下观察肺组织病理学改变,测定肺组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)及髓过氧化物酶(MPO)活性,检测肺组织NF-κB p65和ICAM-1的表达。结果:(1)与Ⅱ/R组比较,Ⅱ-postC组和LⅠ-postC组PaO2升高而PaCO2降低(P<0.05),肺系数减小(P<0.01)且肺组织病理变化减轻;(2)Ⅱ-postC和LⅠ-postC均显著抑制Ⅱ/R所致的肺组织SOD活性降低和MDA含量升高(P<0.05或P<0.01),降低肺组织MPO活性(P<0.01),并下调肺组织NF-κB p65和ICAM-1的表达(P<0.05或P<0.01)。结论:缺血后处理可减轻肠I/R大鼠的肺损伤,其机制可能与抑制NF-κB活化,进而减少ICAM-1介导的中性粒细胞浸润有关。

AIM： To investigate the effect of ischemic postconditioning（I-postC） on the expression of nuclear factor-κB（NF-κB） and intercellular adhesion molecule-1（ICAM-1） in the lungs following intestinal ischemia reperfusion（II/R） in rats,and to explore the possible mechanism of I-postC in attenuating lung injury induced by II/R.METHODS： Thirty-two male Wistar rats were randomly divided into sham,II/R,intestinal ischemic postconditioning（II-postC） and limb ischemic postconditioning（LI-postC） groups.The model of intestinal I/R injury was established by clamping the super mesenteric artery for 45 min followed by 120 min of reperfusion in rats.At the end of the experiment,the changes of arterial blood gas and lung index were measured,and the morphological changes of the lung tissues were observed under light microscope.The content of malondialdehyde（MDA）,the activities of superoxide dismutase（SOD） and myeloperoxidase（MPO） in the lung tissues were also detected.The contents of NF-κB p65 and ICAM-1 in lung tissue were determined by immunohistochemical staining and Western blotting.RESULTS：（1） Compared to those in II/R group,II-postC and LI-postC improved the respiratory functions of the lung,characterized by the increase in PaO2 and decrease in PaCO2（P0.05 vs II/R group）.The lung index was decreased（P0.01） and the pathologic lesion of the lung tissues was alleviated significantly by II-postC and LI-postC.（2） Both II-postC and LI-postC markedly inhibited the decrease in SOD activity,the increase in the content of MDA and the activity of MPO in the lung tissues（P0.05 or P0.01） induced by intestinal I/R.In addition,the over-expression of NF-κB p65 and ICAM-1 in the lung tissues was inhibited markedly by II-postC and LI-postC（P0.05 or P0.01 vs II/R group）.CONCLUSION： I-postC attenuates lung injury induced by intestinal I/R in rats due to suppressing the activation of NF-κB and subsequent accumulation of neutrophils mediated by ICAM-1.