Intraischemic hypothermia differentially modulates oxidative stress proteins during mesenteric ischemia/reperfusion
Intraischemic hypothermia differentially modulates oxidative stress proteins during mesenteric ischemia/reperfusion
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DOI：
10.1067/msy.2002.125722
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发表时间：
2002-08-01
期刊：
影响因子：
3.8
通讯作者：
Moore, FA
中科院分区：
文献类型：
--
作者：
Hassoun, HT;Kozar, RA;Moore, FA
背景胸腹主动脉瘤修复需要强制性肠系膜缺血/再灌注（I/R），引发炎症反应，导致肠道功能障碍和远端器官损伤。在广泛的主动脉手术中，治疗性低温被提倡用于器官保护（即，脑、脊髓和肾脏），并且还被证明可差异性地调节中枢神经系统中的促炎基因转录。在其他I/R模型中，核因子κ B（NF-B-κ）和诱导型一氧化氮合酶（iNOS）恶化，而血红素加氧酶-1（HO-1）保护免受损伤。我们研究了局部缺血内低温对肠系膜I/R诱导的粘膜损伤、NF-κ B活化以及iNOS和HO-1表达的影响。Sprague-Dawley大鼠进行假剖腹术或上级肠系膜动脉闭塞或45分钟，有或没有局部低温（15 ℃-20 ℃）。在再灌注6小时时评估肠上皮对C-14菊粉的渗透性。在一组单独的实验中，在再灌注6小时时获得回肠活检：1）由盲法观察者评估粘膜组织学损伤; 2）通过电泳迁移率变动测定法评估NF-κ B活化; 3）通过免疫印迹法评估iNOS和HO-1蛋白表达。与假手术对照组相比，肠系膜I/R显著增加肠对C-14菊粉的通透性、组织损伤、NF-κ B活化、iNOS和HO-1表达。与此相反，局部低温治疗的大鼠表现出肠道通透性与假手术对照组大鼠，并减少组织损伤。此外，低温可抑制NF-κ B的活化和iNOS的表达，但对HO-1的表达无影响。基于这些观察，我们得出结论，治疗应用缺血内低温保护肠道在肠系膜I/R。此外，低温阻止NF-κ B活化，同时差异调节氧化应激蛋白iNOS和HO-1的表达，以响应肠系膜I/R。
Background. Thoracoabdominal aortic aneurysm repair requires obligatory mesenteric ischemia/reperfusion (I/R), eliciting an inflammatory response resulting in gut dysfunction and remote organ injury. Therapeutic hypothermia has been advocated for organ protection (ie, brain, spinal cord, and kidneys) during extensive aortic operation, and it has also been shown to diffrentially modulate pro-inflammatory gene transcription in the central nervous system. In other I/R models, nuclear factor Kappa-B (NF-B-kappa) and inducible nitric oxide synthase (iNOS) worsen while heme oxygenase-1 (HO-1) protects against injury. We examined the effects of regional intraischemic hypothermia on mesenteric I/R-induced mucosal injury, NF-kappaB activation, and expression of iNOS and HO-1.Methods. Sprague-Dawley rats underwent sham laparotomy or superior mesenteric artery occlusion or 45 minutes with or without topical hypothermia (15degrees-20degreesC). Intestinal epithelial permeability to C-14 inulin was assessed at 6 hours of reperfusion. In a separate set of experiments, biopsies of the ileum were obtained at 6 hours of reperfusion for: 1) mucosal histologic injury assessed by a blinded observer; 2) NF-kappaB activation by electrophoretic mobility shift assay; and 3) iNOS and HO-1 protein expression by immunoblot.Results. Mesenteric I/R significantly increased intestinal permeability to C-14 inulin, histologic injury, activation of NF-kappaB, and iNOS and HO-1 expression when compared with sham control rats. In contrast, rats treated with intraischemic topical hypothermia exhibited intestinal permeability comparable with sham control rats, and reduced histologic injury. In addition, hypothermia prevented the activation of NF-kappaB and iNOS expression, but had no effect on HO-1 expression.Conclusions. On the basis of these observations, we conclude that therapeutically applied intraischemic hypothermia protects the gut during mesenteric I/R. In addition, hypothermia prevented NF-kappaB activation while differentially modulating expression of the oxidative stress proteins iNOS and HO-1 in response to mesenteric I/R.