Department of Anesthesiology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510000, China.
Oxid Med Cell Longev. 2018 Oct 28;2018:4780615. doi: 10.1155/2018/4780615. eCollection 2018.
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.
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.
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-, IL-1, IL-6, TLR4, and NF-B inflammatory pathway, accompanied with decrease of neutrophil elastase activity, MPO activity, 8-isoprotane, p47 and gp91 protein expressions, and increase of SOD activity. Inhibition of Nox2 by VAS2870 conferred similar protective effects in liver transplantation.
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.
肝移植导致肝脏缺血/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。静脉麻醉异丙酚对自由基清除具有强大作用，并能保护肝脏免受 I/R 损伤。然而，异丙酚介导的肝保护在肝移植中的作用和机制尚不清楚。本研究旨在评估异丙酚后处理在肝移植后肝 I/R 损伤中的作用。
48 只大鼠随机分为六组：接受假手术或原位自体肝移植（OALT）的大鼠，在不存在或存在异丙酚（高剂量和低剂量）后处理或脂肪乳对照或 VAS2870（Nox2 特殊抑制剂）的情况下。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。
OALT 后，观察到严重的肝病理损伤，血清 AST 和 ALT 升高，异丙酚后处理可减轻损伤。此外，特别是高剂量异丙酚后处理可降低 TNF-α、IL-1、IL-6、TLR4 和 NF-B 炎症途径，同时降低中性粒细胞弹性蛋白酶活性、MPO 活性、8-异前列腺素、p47 和 gp91 蛋白表达，增加 SOD 活性。Nox2 抑制 VAS2870 可在肝移植中产生类似的保护作用。
肝移植导致严重的炎症和氧化应激，伴有 NADPH 氧化酶的激活。异丙酚后处理部分通过抑制 NADPH 氧化酶 Nox2 及其随后的炎症和氧化应激来减轻肝移植后的肝 I/R 损伤。
