Liu Yi, Du Xiaohong, Zhang Shouhua, Liu Xiuxia, Xu Guohai
Department of Anesthesiology, Second Affiliated Hospital of Nanchang University Nanchang 330006, China.
Jiangxi Province Key Laboratory of Anesthesiology Nanchang 330006, China.
Int J Clin Exp Pathol. 2017 Nov 1;10(11):10959-10968. eCollection 2017.
Propofol exerts protective effects on multiple organs, including the liver. The aim of the present study was to investigate whether the protective effects of propofol on the liver are related to Sirt1, an NAD-dependent deacetylase with anti-inflammatory and antioxidant properties.
After treatment with propofol, hepatic I/R injury was induced in mice. Liver injury, oxidative stress, antioxidant capacity, cytokine production, and apoptotic markers were investigated to assess the effects of propofol pretreatment on hepatic I/R injury. The expression of Sirt1 was assessed by immunohistochemical and western blot analyses, and the expression levels of NF-κB/p65, IκBα, Bcl-2 and Bax were analyzed by western blot.
After 70% hepatic I/R injury, the mice that were pretreated with propofol showed considerably less liver injury, enhanced anti-inflammatory and antioxidant capacity, and less apoptosis. Additional studies revealed that propofol pretreatment prior to I/R injury results in reduced NF-κB activation and apoptosis through Sirt1 activation.
The present study is the first to reveal that propofol can significantly reduce hepatic I/R injury by regulating the expression of Sirt1, and these effects may be related to anti-inflammatory and antioxidant effects. Our results suggest that propofol may be an effective therapeutic strategy for the treatment of hepatic I/R injury in hepatobiliary surgery.
丙泊酚对包括肝脏在内的多个器官具有保护作用。本研究的目的是探讨丙泊酚对肝脏的保护作用是否与沉默调节蛋白1（Sirt1）有关，Sirt1是一种具有抗炎和抗氧化特性的烟酰胺腺嘌呤二核苷酸（NAD）依赖性脱乙酰酶。
用丙泊酚处理小鼠后，诱导其发生肝脏缺血/再灌注（I/R）损伤。研究肝脏损伤、氧化应激、抗氧化能力、细胞因子产生及凋亡标志物，以评估丙泊酚预处理对肝脏I/R损伤的影响。通过免疫组织化学和蛋白质印迹分析评估Sirt1的表达，通过蛋白质印迹分析NF-κB/p65、IκBα、Bcl-2和Bax的表达水平。
在70%肝脏I/R损伤后，丙泊酚预处理的小鼠肝脏损伤明显减轻，抗炎和抗氧化能力增强，凋亡减少。进一步研究表明，I/R损伤前丙泊酚预处理通过激活Sirt1减少NF-κB激活和凋亡。
本研究首次揭示丙泊酚可通过调节Sirt1的表达显著减轻肝脏I/R损伤，这些作用可能与抗炎和抗氧化作用有关。我们的结果表明，丙泊酚可能是肝胆手术中治疗肝脏I/R损伤的有效治疗策略。
