NBD Peptides Protect Against Ischemia Reperfusion After Orthotopic Liver Transplantation in Rats
NBD Peptides Protect Against Ischemia Reperfusion After Orthotopic Liver Transplantation in Rats
复制标题
NBD 肽可防止大鼠原位肝移植后的缺血再灌注。
DOI：
10.1016/j.jss.2011.12.005
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发表时间：
2012-08-01
影响因子：
2.2
通讯作者：
Liu, Chang-an
中科院分区：
文献类型：
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作者：
Cheng, Ming-xiang;Gong, Jian-ping;Liu, Chang-an
背景NBD（NEMO binding domain，NEMO结合域）肽能选择性抑制炎症诱导的NF-κ B活性，而不影响NF-κ B的保护作用。本研究的目的是确定NBD肽是否抑制核因子-κ B（NF-κ B）在肝移植缺血-再灌注损伤（IRI）的转录活性，而不影响其基础功能。采用Kamada法建立SD大鼠原位肝移植模型，建立道利（SD）大鼠原位肝移植模型。供体在手术前2 h给予NBD肽（8 mg/kg，腹膜内）（n = 24），对照用相同体积的生理盐水处理（n = 24）。将另外16只处于正常状态的动物（未进行任何手术）也分成两组，并给予与上述相同的治疗，以评估NBD肽对基础功能的影响。我们分析了门静脉再灌注后3、6和24 h以及正常情况下（n = 8）肝组织的丙氨酸氨基转移酶（ALT）、肿瘤坏死因子（TNF-α）、IKK（I κ B激酶）复合物磷酸化、I κ B α降解、NF-κ B转录活性、细胞凋亡水平，并进行了形态学研究。NBD肽预处理可通过下调TNF-α水平、抑制IKK复合物磷酸化、I κ B α降解和NF-κ B转录活性，显著改善肝功能，减轻肝实质细胞损伤和凋亡，但在正常情况下无影响。NBD肽通过阻止NF-κ B活化而减弱肝IRI，而不影响基础NF-κ B活性。(C)2012 Elsevier Inc. All rights reserved.
Background. NBD (NEMO binding domain) peptides could selectively inhibit the inflammation induced NF-kappa B activity, while sparing the protective functions of basal NF-kappa B activity. The aim of this study was to determine whether NBD peptides inhibited the transcriptional activity of nuclear factor-kappa B (NF-kappa B) during liver transplant ischemia-reperfusion injury (IRI), without affecting its basal function.Materials and Methods. Sprague Dawley (SD) rats were performed orthotropic liver transplantation according to the Kamada technique. Donors were given NBD peptides (8 mg/kg, intraperitoneal) 2 h before surgery (n = 24) and the controls were treated with the same volume of physiologic saline (n = 24). An additional 16 animals in normal condition (did not undergo any surgery) were also divided into two groups and given the same treatment as above to assess the effect of NBD peptides on basal function. We analyzed levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF-alpha), IKK (I kappa B kinase) complex phosphorylation, I kappa B alpha degradation, NF-kappa B transcriptional activity, apoptosis, and performed a morphologic study of liver tissues at 3, 6, and 24 h after portal vein reperfusion and in normal condition (n = 8).Results. Pretreatment with NBD peptides significantly improved liver function, attenuating liver parenchymal cell damage, apoptosis by down-regulating TNF-alpha level, inhibiting IKK complex phosphorylation, I kappa B alpha degradation, and NF-kappa B transcriptional activity, but had no effect in normal condition.Conclusion. NBD peptides attenuated hepatic IRI by preventing NF-kappa B activation, without affecting basal NF-kappa B activity. (C) 2012 Elsevier Inc. All rights reserved.