Intravenous Anesthetic Protects Hepatocyte from Reactive Oxygen Species-Induced Cellular Apoptosis during Liver Transplantation In Vivo
Intravenous Anesthetic Protects Hepatocyte from Reactive Oxygen Species-Induced Cellular Apoptosis during Liver Transplantation In Vivo
复制标题
静脉麻醉药可保护肝细胞免受体内肝移植过程中活性氧诱导的细胞凋亡的影响。
DOI：
10.1155/2018/4780615
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Hei，Ziqing
中科院分区：
文献类型：
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作者：
Yao，Weifeng;Han，Xue;Hei，Ziqing
背景肝移植会导致肝脏缺血/再灌注（I/R）损伤，导致早期移植物功能障碍和衰竭。氧化应激和炎症反应的加剧是肝I/R损伤发展的关键过程。静脉麻醉药异丙酚具有清除自由基和保护肝脏的作用。然而，丙泊酚介导的肝保护在肝移植中的作用和机制知之甚少。本研究旨在探讨丙泊酚后处理在肝移植术后肝I/R损伤中的作用。将48只大鼠随机分为6组：在不存在或存在丙泊酚（高剂量和低剂量）后处理或内毒素对照或VAS 2870（Nox 2特异性抑制剂）的情况下接受假手术或原位自体肝移植（OALT）的大鼠。OALT或假手术后8小时，评估器官损伤、氧化应激、炎症和NADPH相关蛋白的参数。在OALT后，观察到严重的肝脏病理损伤，与血清AST和ALT升高相关，这被丙泊酚后处理减弱。此外，特别是高剂量丙泊酚后处理降低了TNF-α、IL-1β、IL-6、TLR 4和NF-κB炎症通路，同时降低了中性粒细胞弹性蛋白酶活性、MPO活性、8-isoprotane、p47 phox和gp 91 phox蛋白表达，增加了SOD活性。VAS 2870抑制Nox 2在肝移植中具有相似的保护作用。肝移植导致严重的炎症和氧化应激与NADPH氧化酶激活。异丙酚后处理可减轻肝移植术后I/R损伤，其机制可能与抑制NADPH氧化酶Nox 2及随后的炎症反应和氧化应激有关。
Background. Liver transplantation leads to liver ischemia/reperfusion (I/R) injury, resulting in early graft dysfunction and failure. Exacerbations of oxidative stress and inflammatory response are key processes in the development of liver I/R injury. Intravenous anesthetic propofol potent effects on free radical scavenging and protects livers against I/R injury. However, the role and mechanism of propofol‐mediated hepatic protection in liver transplantation is poorly understood. The aim of this study was to evaluate the role of propofol postconditioning in the liver I/R injury after liver transplantation.Methods. Forty‐eight rats were randomly divided into six groups: rats receiving either sham operation or orthotopic autologous liver transplantation (OALT) in the absence or presence of propofol (high dose and low dose) postconditioning or intralipid control or VAS2870 (Nox2 special inhibitor). Eight hours after OALT or sham operation, parameters of organ injury, oxidative stress, inflammation, and NADPH‐associated proteins were assessed.Results. After OALT, severe liver pathological injury was observed that was associated with increases of serum AST and ALT, which were attenuated by propofol postconditioning. In addition, especially high dose of propofol postconditioning reduced TNF‐α, IL‐1β, IL‐6, TLR4, and NF‐κB inflammatory pathway, accompanied with decrease of neutrophil elastase activity, MPO activity, 8‐isoprotane, p47phoxand gp91phoxprotein expressions, and increase of SOD activity. Inhibition of Nox2 by VAS2870 conferred similar protective effects in liver transplantation.Conclusion. Liver transplantation leads to severe inflammation and oxidative stress with NADPH oxidase activation. Propofol postconditioning reduces liver I/R injury after liver transplantation partly via inhibiting NADPH oxidase Nox2 and the subsequent inflammation and oxidative stress.