环氧合酶-2在小肠缺血再灌注损伤中对免疫状态的影响

背景：小肠缺血再灌注（I／R）是危重症过程中常见的病理改变，研究其损伤发生机制对多器官功能障碍综合征的防治具有重要意义。目的：探讨COX-2在小肠I／R损伤中对免疫状态的影响。方法：48只大鼠随机分为假手术组（n=8）、I／R模型组（n=20）和COX-2选择性抑制剂尼美舒利干预组（n=20），干预组于造模前1h予尼美舒利80mg／kg灌胃。各组分别于再灌注3、6、12、24h后采集标本，行小肠组织COX-2mRNA、血清D-乳酸、血清促炎（IL-6、TNF-a）和抗炎（IL-10）细胞因子以及全血T细胞亚群检测。结果：I／R模型组小肠组织COX-2mRNA表达、血清D-乳酸水平在再灌注后3h即明显增高，6h时达峰值，各时点均显著高于假手术组（P〈0．05），同时血清IL-6、TNF-a、IL-10水平显著增高（P〈0．05），全血CD4＋／CD8＋比值持续降低（P〈0．05）。与同时点I／R模型组相比，尼美舒利干预组COX-2mRNA表达、D哥L酸水平显著降低（P〈0．05），IL-10水平、CD4＋／CD8＋比值显著增高（P〈0．05），IL-6、TNF-a水平略有降低。结论：COX-2在小肠I／R损伤中发挥重要作用，其机制可能为改变促炎／抗炎细胞因子之间以及CD4＋／CD8＋细胞之间的动态平衡，即同时作用于非特异性和特异性免疫系统，导致严重的机体免疫状态紊乱。COX-2选择性抑制剂可能系通过抗炎和免疫调节作用改善小肠I／R损伤。

Effect of Cyclooxygenase-2 on Immune Status in Small Bowel Ischemia-reperfusion Injury

Background： Small bowel ischemia-reperfusion （I/R） is a common pathological change in critical care medicine, thus it is of great importance to study the underlying mechanism of I/R injury for prevention and management of multiple organ dysfunction syndrome. Aims： To investigate the effect of COX-2 on immune status in small bowel I/R injury. Methods ： Forty-eight rats were randomly divided into three groups ： sham operated group （ n = 8 ） , I/R model group （ n = 20） and nimesulide （a COX-2 selective inhibitor） intervention group （n = 20）. In intervention group, nimesulide 80 mg/ kg was administered intragastrically 1 hour before model construction. Blood and intestinal tissue samples were obtained 3, 6, 12 and 24 hours, respectively, after reperfusion. COX-2 mRNA in intestinal tissues, as well as serum D-lactic acid, serum proinflammatory （IL-6 and TNF-a） and anti-inflammatory cytokines （IL-10） , and whole blood T cell subsets were measured. Results ： In I/R model group, increase of intestinal COX-2 mRNA and serum D-lactic acid initiated at the early stage of reperfusion （3 h） and reached the peak at 6 h, and at all time points were significantly higher than those in sham operated group （ P 〈 0.05 ） ; serum IL-6, TNF-a and IL-10 increased simultaneously （ P 〈 0.05 ） , and whole blood CD4＋/CD8＋ ratio decreased continuously （ P 〈 0.05 ）. When compared with I/R model group at the same time point, COX-2 mRNA and D-lactic acid decreased significantly （ P 〈 0. 05 ） and IL-10 and CD4＋/CD8＋ ratio increased significantly （ P 〈 0.05 ） in nimesulide intervention group ; IL-6 and TNF-a in intervention group only had a little decrease. Conclusions： COX-2 might play an important role in small bowel I/R injury by altering the dynamic equilibrium between pro-/anti-inflammatory cytokines and CD4＋/CD8＋ cells, in other words, by affecting nonspecific and specific immunity simultaneously, ultimately leading to severe immunological disorder. COX-2 selective inhibitor can attenuate small bowel I/R injury through its antiinflammatory and immunomodulatory effects.