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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >The role of excessive versus acute administration of erythropoietin in attenuating hepatic ischemia-reperfusion injury.
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The role of excessive versus acute administration of erythropoietin in attenuating hepatic ischemia-reperfusion injury.

机译:过度和急性给予促红细胞生成素在减轻肝脏缺血再灌注损伤中的作用。

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Ischemia-reperfusion injury (I/R) is the main cause of primary graft nonfunction. Our aim was to evaluate the effect of excessive versus acute administration of erythropoietin (EPO) in attenuating the hepatic injury induced by I/R in mice. The effect of segmental (70%) hepatic ischemia was evaluated in a transgenic mouse line with constitutive overexpression of human EPO cDNA and in wild-type (WT) mice. Mice were randomly allocated to 5 main experimental groups: (i) WT-sham, (ii) WT ischemia, (iii) WT ischemia + recombinant human erythropoietin (rhEPO), (iv) transgenic-sham, and (v) transgenic ischemia. The EPO-pretreated mice showed a significant reduction in liver enzyme levels and intrahepatic caspase-3 activity and fewer apoptotic hepatocytes (p < 0.05 for all) compared with the WT untreated I/R group. EPO decreased c-Jun N-terminal kinase (JNK) phosphorylation and nuclear factor-kappaB (NF-kappaB) expression during I/R. In transgenic I/R livers, baseline histology showed diffused hepatic injury, and no significant beneficial effect was noted between the WT untreated and the transgenic I/R mice. In conclusion, acute pretreatment with EPO in WT mice attenuated in vivo I/R liver injury. However, in excessive EPO overexpression, the initial liver injury abolished the beneficial effect of EPO. These findings have important implications for the potential use of acute EPO in I/R injury during liver transplantation.
机译:缺血-再灌注损伤(I / R)是原发性移植物失灵的主要原因。我们的目的是评估过量和急性给予促红细胞生成素(EPO)在减轻小鼠I / R诱导的肝损伤中的作用。在具有组成型过表达人EPO cDNA的转基因小鼠品系和野生型(WT)小鼠中评估了节段性(70%)肝缺血的作用。将小鼠随机分为5个主要实验组:(i)野生型假手术,(ii)野生型缺血,(iii)野生型缺血+重组人促红细胞生成素(rhEPO),(iv)转基因假性,和(v)转基因缺血。与WT未处理的I / R组相比,经EPO预处理的小鼠显示出肝酶水平和肝内caspase-3活性显着降低,并且凋亡的肝细胞更少(所有p <0.05)。在I / R期间,EPO降低了c-Jun N末端激酶(JNK)的磷酸化和核因子-kappaB(NF-kappaB)的表达。在转基因I / R肝脏中,基线组织学表现为弥漫性肝损伤,在未治疗的WT和转基因I / R小鼠之间未观察到明显的有益作用。总之,在WT小鼠中用EPO进行急性预处理可减轻体内I / R肝损伤。但是,在过度的EPO过表达中,最初的肝损伤消除了EPO的有益作用。这些发现对在肝移植过程中急性EPO在I / R损伤中的潜在用途具有重要意义。

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