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首页> 外文期刊>Biomedical Journal >The protective role of IL-1Ra on intestinal ischemia reperfusion injury by anti-oxidative stress via Nrf2/HO-1 pathway in rat
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The protective role of IL-1Ra on intestinal ischemia reperfusion injury by anti-oxidative stress via Nrf2/HO-1 pathway in rat

机译:IL-1Ra通过Nrf2 / HO-1途径抗氧化应激对大鼠肠缺血再灌注损伤的保护作用

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Background Intestinal ischemia reperfusion injury is a frequent clinical damage, in which the oxidative stress and inflammation play an important role. Interleukin-1 receptor antagonist (IL-1Ra) is a natural anti-inflammatory factor, however, its effect on intestinal ischemia reperfusion injury remains unclear. Methods The rat model of intestinal I/R was induced by occlusion (for 60?min) and reopening (for 60?min) of superior mesenteric artery. The rats were randomly divided into the following 5 groups: sham-operation(S), model (I/R),10?mg/kgIL-1Ra?+?I/R (C1),20?mg/kgIL-1Ra?+?I/R (C2), and30?mg/kgIL-1Ra?+?I/R (C3). Results In this study it was the first time to confirm that IL-1Ra had a significant protection against the intestinal ischemia reperfusion injury. IL-1Ra not only effectively inhibited the expression of inflammatory factors (such as IL-1β, IL-6 and TNF-α) and the activation of neutrophil in intestinal tissues, but also decreased the death of intestinal cells and the damages of intestinal tissues. Interestingly, besides anti-inflammation effect, it was also found that IL-1Ra possessed a significant inhibitory effect on the oxidative stress caused by ischemia/reperfusion injury. Furthermore, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1), and the phosphorylation level of Nrf2 were greatly promoted by IL-1Ra. At the same time, IL-1Ra inhibited the mitogen-activated protein kinase (MAPKs) pathway. Conclusion IL-1Ra had the protective effect against intestinal ischemia reperfusion injury, its mechanism included anti-inflammation and anti-oxidative stress in which the Nrf2/HO-1 pathway played an important role. The above-mentioned results may extend the clinical application of IL-1Ra in the treatment of intestinal ischemia reperfusion injury.
机译:背景技术肠缺血再灌注损伤是一种常见的临床损伤,其中氧化应激和炎症起重要作用。白介素-1受体拮抗剂(IL-1Ra)是一种天然的抗炎因子,但是,其对肠缺血再灌注损伤的作用尚不清楚。方法通过肠系膜上动脉闭塞(60?min)并再张开(60?min)诱导大鼠肠I / R模型。将大鼠随机分为以下5组:假手术(S),模型(I / R),10μmg/ kgIL-1Ra 2 +ΔI/ R(C1),20μmg/ kgIL-1Ra 2。 +ΔI/ R(C2)和30μmg/kgIL-1Raα+ΔI/ R(C3)。结果在本研究中,这是首次证实IL-1Ra对肠缺血再灌注损伤具有显着保护作用。 IL-1Ra不仅能有效抑制肠道组织中炎症因子(如IL-1β,IL-6和TNF-α)的表达和嗜中性粒细胞的活化,而且还能减少肠道细胞的死亡和肠道组织的损伤。 。有趣的是,除了抗炎作用外,还发现IL-1Ra对由缺血/再灌注损伤引起的氧化应激具有显着的抑制作用。此外,IL-1Ra大大促进了核因子红系2相关因子2(Nrf2)和血红素加氧酶1(HO-1)的表达以及Nrf2的磷酸化水平。同时,IL-1Ra抑制有丝分裂原激活的蛋白激酶(MAPKs)途径。结论IL-1Ra对肠缺血再灌注损伤具有保护作用,其机制包括抗炎和抗氧化应激,其中Nrf2 / HO-1途径起重要作用。上述结果可扩展IL-1Ra在治疗肠缺血再灌注损伤中的临床应用。

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