Ge Mian, Yao Weifeng, Wang Yanling, Yuan Dongdong, Chi Xinjin, Luo Gangjian, Hei Ziqing
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
J Surg Res. 2015 Jun 15;196(2):373-81. doi: 10.1016/j.jss.2015.03.016. Epub 2015 Mar 19.
Nuclear factor-E2-related factor 2 (Nrf2)-mediated antioxidant response is the main protective system of graft-liver against ischemia-reperfusion injury after liver transplantation. Propofol is considered to confer protective effects on different organs; thus, we explored the possibility that whether propofol could attenuate graft-liver injury in a rat autologous orthotopic liver transplantation (AOLT) model and mechanisms were associated with activation of Nrf2 pathway.
Sprague-Dawley rats were randomly divided into four groups: sham-operated group, saline-treated AOLT group, low-dose propofol intervention group, and high-dose propofol intervention group. Liver injury was determined, and concentration of hydroxyl free radical (•OH), superoxide anion (O2(•-)), and malondialdehyde in the liver tissue were detected. The expression of Keap1, Nrf2, HO-1, and NQO1 were explored by Western blotting, and also the change of Nrf2 and keap1 was assessed by immunofluorescence.
Compared with sham group, pathologic damage of graft-livers was in a time-dependent manner, accompanied with the increased level of oxidative stress in the AOLT group, and nuclear Nrf2 expression and its downstream antioxidant enzyme, HO-1 and NQO1, were also increased in this group. However, in propofol pretreatment groups especially in the high-dose group, the pathologic score was significantly decreased, accompanied with a lower level of •OH, O2(•-), and malondialdehyde than that of the AOLT group. The change of oxidative stress might be related to the Nrf2 pathway, evidenced as the elevation of protein expression level of NQO1, HO-1, and nuclear Nrf2.
Protective effects of propofol against liver transplantation-induced graft-liver injury may be related with Keap1-Nrf2 signal pathway activation.
核因子E2相关因子2（Nrf2）介导的抗氧化反应是移植肝脏对抗肝移植后缺血再灌注损伤的主要保护系统。丙泊酚被认为对不同器官具有保护作用；因此，我们探讨了丙泊酚是否能减轻大鼠自体原位肝移植（AOLT）模型中的移植肝损伤，以及其机制是否与Nrf2信号通路的激活有关。
将Sprague-Dawley大鼠随机分为四组：假手术组、生理盐水处理的AOLT组、低剂量丙泊酚干预组和高剂量丙泊酚干预组。测定肝损伤情况，并检测肝组织中羟自由基（•OH）、超氧阴离子（O2(•-)）和丙二醛的浓度。通过蛋白质免疫印迹法检测Keap1、Nrf2、HO-1和NQO1的表达，并通过免疫荧光法评估Nrf2和Keap1的变化。
与假手术组相比，移植肝的病理损伤呈时间依赖性，AOLT组氧化应激水平升高，该组中核Nrf2表达及其下游抗氧化酶HO-1和NQO1也增加。然而，在丙泊酚预处理组尤其是高剂量组中，病理评分显著降低，与AOLT组相比，•OH、O2(•-)和丙二醛水平更低。氧化应激的变化可能与Nrf2信号通路有关，表现为NQO1、HO-1和核Nrf2蛋白表达水平升高。
丙泊酚对肝移植引起的移植肝损伤的保护作用可能与Keap1-Nrf2信号通路的激活有关。
