Butyrate protects liver against ischemia reperfusion injury by inhibiting nuclear factor kappa B activation in Kupffer cells
Butyrate protects liver against ischemia reperfusion injury by inhibiting nuclear factor kappa B activation in Kupffer cells
复制标题
丁酸盐通过抑制 Kupffer 细胞中核因子 kappa B 的激活来保护肝脏免受缺血再灌注损伤
DOI：
10.1016/j.jss.2013.08.028
复制
发表时间：
2014-04-01
影响因子：
2.2
通讯作者：
Wang, Qian-wei
中科院分区：
文献类型：
--
作者：
Qiao, Ying-li;Qian, Jian-min;Wang, Qian-wei
背景：肝缺血再灌注（I/R）后的炎症反应导致移植后肝功能障碍和衰竭。丁酸盐是一种四碳脂肪酸，通常由哺乳动物肠道中的纤维细菌发酵产生，具有抗炎活性。本研究的目的是探讨丁酸盐预处理（如果有的话）对大鼠肝缺血再灌注损伤的保护作用及其相关机制。 方法：雄性 Sprague-Dawley 大鼠在用载体或丁酸盐预处理后进行部分（0%）肝缺血 60 分钟，然后再灌注 3、6 和 24 小时。通过生化和组织病理学检查评估肝损伤。通过髓过氧化物酶（MPO）活性来测量中性粒细胞浸润。通过酶联免疫吸附测定（Elisa）和实时逆转录酶聚合酶链反应（RT-PCR）测量肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的表达。通过免疫组织化学和蛋白质印迹分析测定核因子kappa B (NF-kB) p65的表达。结果：丁酸盐治疗显着改善肝功能和组织学，转氨酶水平降低和组织病理变化改善。丁酸盐减弱了肿瘤坏死因子-α、白细胞介素-6 的表达和髓过氧化物酶活性。丁酸盐还可以减少缺血再灌注诱导的库普弗细胞中 NF-kB p65 的核易位。结论：我们的结果表明，丁酸盐可能通过抑制炎症因子的产生并防止库普弗细胞中 NF-kB 的激活来减轻缺血再灌注诱导的肝损伤。 (C) 2014 年，爱思唯尔公司出版
Background: The inflammatory response after hepatic ischemia reperfusion (I/R) contributes to liver dysfunction and failure after transplantation. Butyrate is a four-carbon fatty acid, normally produced by bacterial fermentation of fiber in mammalian intestines, with antiinflammatory activities. The purpose of the present study was to investigate the protective effect of butyrate preconditioning, if any, against hepatic I/R injury in rats and the underlying mechanisms involved.Methods: Male Sprague-Dawley rats were subjected to a partial ( 0%) hepatic ischemia for 60 min after pretreatment with either vehicle or butyrate, followed by 3, 6, and 24 h of reperfusion. Hepatic injury was evaluated by biochemical and histopathologic examinations. Neutrophil infiltration was measured by myeloperoxidase (MPO) activity. The expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (Elisa) and Real- time reverse- transcriptase polymerase chain reaction (RT-PCR). The expression of nuclear factor kappa B (NF-kB) p65 was determined by immunohistochemistry and Western blot analysis.Results: Butyrate treatment markedly improved hepatic function and histology, as indicated by reduced transaminase levels and ameliorated tissue pathologic changes. The expression of tumor necrosis factor- alpha, interleukin-6, and myeloperoxidase activity was attenuated by butyrate. Butyrate also reduced I/R-induced nuclear translocation of NF-kB p65 in Kupffer cells.Conclusion: Our results suggest that butyrate alleviates I/R-induced liver injury, possibly by suppressing inflammatory factors production and preventing NF-kB activation in Kupffer cells. (C) 2014 Published by Elsevier Inc.