Carbon Monoxide Liberated from CO-Releasing Molecule (CORM-2) Attenuates Ischemia/Reperfusion (I/R)-Induced Inflammation in the Small Intestine
Carbon Monoxide Liberated from CO-Releasing Molecule (CORM-2) Attenuates Ischemia/Reperfusion (I/R)-Induced Inflammation in the Small Intestine
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DOI：
10.1007/s10753-009-9162-y
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发表时间：
2010-04-01
期刊：
影响因子：
5.1
通讯作者：
Cepinskas, Gediminas
中科院分区：
文献类型：
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作者：
Katada, Kazuhiro;Bihari, Aurelia;Cepinskas, Gediminas
corm释放的CO已被证明对急性炎症的解决是有益的。肠缺血再灌注（I/R）损伤的急性期以氧化应激相关炎症和白细胞募集为特征。在这项研究中，我们评估了corm -2释放的CO在I/ r刺激后小肠炎症反应调节中的作用和潜在机制。为此，通过阻断肠系膜上动脉（SMA）对小鼠（C57Bl/6）小肠缺血45 min。在SMA闭塞前立即给予CORM-2 （8mg /kg；静脉注射）。假手术小鼠注射载药（0.25% DMSO）。再灌注后4小时，通过测量组织中tnf - α蛋白（ELISA）、粘附分子e -选择素和ICAM-1 （Western blot）、NF-kappa B激活（EMSA）水平、PMN组织积累（MPO测定）和空肠微循环中白细胞滚动/粘附（活体显微镜）来评估小肠（空肠）的炎症反应。结果表明，I/ r刺激空肠组织中tnf - α、e -选择素和ICAM-1蛋白的表达水平、nf - κ B的激活以及随后PMN的积累均升高。在corm -2处理的小鼠中，上述变化明显减弱。综上所述，这些研究结果表明，corm -2释放的CO通过干扰I/ r挑战小肠中nf - κ B的激活和随后的血管促粘附表型上调来发挥抗炎作用。
CORM-released CO has been shown to be beneficial in resolution of acute inflammation. The acute phase of intestinal ischemia-reperfusion (I/R) injury is characterized by oxidative stress-related inflammation and leukocyte recruitment. In this study, we assessed the effects and potential mechanisms of CORM-2-released CO in modulation of inflammatory response in the small intestine following I/R-challenge. To this end mice (C57Bl/6) small intestine were challenged with ischemia by occluding superior mesenteric artery (SMA) for 45 min. CORM-2 (8 mg/kg; i.v.) was administered immediately before SMA occlusion. Sham operated mice were injected with vehicle (0.25% DMSO). Inflammatory response in the small intestine (jejunum) was assessed 4 h following reperfusion by measuring tissue levels of TNF-alpha protein (ELISA), adhesion molecules E-selectin and ICAM-1 (Western blot), NF-kappa B activation (EMSA), along with PMN tissue accumulation (MPO assay) and leukocyte rolling/adhesion in the microcirculation of jejunum (intravital microscopy). The obtained results indicate that tissue levels of TNF-alpha, E-selectin and ICAM-1 protein expression, activation of NF-kappa B, and subsequent accumulation of PMN were elevated in I/R-challenged jejunum. The above changes were significantly attenuated in CORM-2-treated mice. Taken together these findings indicate that CORM-2-released CO confers anti-inflammatory effects by interfering with NF-kappa B activation and subsequent up-regulation of vascular pro-adhesive phenotype in I/R-challenged small intestine.