首页> 外文期刊>The Journal of toxicological sciences >Inhibiton of NF-kappaB activation during ischemia reduces hepatic ischemia/reperfusion injury in rats.
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Inhibiton of NF-kappaB activation during ischemia reduces hepatic ischemia/reperfusion injury in rats.

机译:缺血期间抑制NF-κB活化可减少大鼠肝缺血/再灌注损伤。

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摘要

The aim of this study was to determine whether nuclear factor-kappaB (NF-kappaB) inhibitors are efficient against hepatic ischemia/reperfusion (I/R) injury. We previously demonstrated that xanthine oxidase-derived reactive oxygen species activate NF-kappaB during ischemia. However, the role of NF-kappaB activation during ischemia in post-reperfusion injury remains unclear. Therefore, while we examined the effects of NF-kappaB inhibitors, sulfasalazine and pyrrolidinedithiocarbamate on hepatic I/R injury using a rat lobar hepatic I/R model, we estimated the relationship between NF-kappaB activation during ischemia and following hepatic damage caused by reperfusion. The portal vein and the hepatic artery were clamped for 1 hr followed by reperfusion for up to 24 hr. NF-kappaB activation was determined by Western blot analysis. NF-kappaB activation was observed in the ischemic lobe of the liver, and the activation was prevented by pre-administration with NF-kappaB inhibitors. Although the serum ALT level,hepatic MPO activity and BSP clearance, as an index of hepatic injury, were increased after reperfusion, the increase was attenuated by pre-administration with NF-kappaB inhibitors. These findings suggest that NF-kappaB activation during ischemia is relevant to hepatic I/R injury. Moreover, we first showed that pre-administration with NF-kappaB inhibitors is effective against hepatic I/R injury.
机译:这项研究的目的是确定核因子-κB(NF-kappaB)抑制剂对肝缺血/再灌注(I / R)损伤是否有效。我们以前证明黄嘌呤氧化酶衍生的活性氧在缺血过程中激活NF-κB。然而,NF-κB激活在缺血后再灌注损伤中的作用尚不清楚。因此,虽然我们使用大鼠大叶肝I / R模型检查了NF-κB抑制剂,柳氮磺吡啶和吡咯烷二硫代氨基甲酸酯对肝I / R损伤的影响,但我们估计了缺血期间和再灌注引起的肝损伤后NF-κB活化之间的关系。 。将门静脉和肝动脉夹紧1小时,然后再灌注长达24小时。通过蛋白质印迹分析确定NF-κB的活化。在肝脏的缺血性叶中观察到NF-kappaB的激活,并且通过预先服用NF-kappaB抑制剂可阻止该激活。再灌注后,虽然血清ALT,肝MPO活性和BSP清除率(作为肝损伤的指标)有所增加,但预先给予NF-κB抑制剂可减轻这种增加。这些发现表明,缺血期间NF-κB的活化与肝I / R损伤有关。此外,我们首先表明与NF-κB抑制剂一起预给药对肝I / R损伤有效。

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