Propofol alleviates liver oxidative stress via activating Nrf2 pathway
Propofol alleviates liver oxidative stress via activating Nrf2 pathway
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异丙酚通过激活Nrf2通路减轻肝脏氧化应激
DOI：
10.1016/j.jss.2015.03.016
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发表时间：
2015-06-15
影响因子：
2.2
通讯作者：
Hei, Ziqing
中科院分区：
文献类型：
--
作者：
Ge, Mian;Yao, Weifeng;Hei, Ziqing
背景资料：核因子E2相关因子2（Nrf 2）介导的抗氧化反应是肝移植术后移植肝抗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）模型中移植肝损伤的可能性，其机制与Nrf 2通路的激活有关。假手术组、生理盐水处理AOLT组、小剂量丙泊酚干预组、大剂量丙泊酚干预组。检测肝组织中羟自由基（中心点OH）、超氧阴离子（O-2（中心点-））和丙二醛（MDA）含量。Western blotting检测Keap 1、Nrf 2、HO-1、NQO 1的表达，免疫荧光检测Nrf 2、Keap 1的变化。与假手术组相比，AOLT组移植肝病理损伤呈时间依赖性，并伴有氧化应激水平升高，核Nrf 2及其下游抗氧化酶HO-1和NQO 1表达增加，在这一组中也有所增加。而异丙酚预处理组尤其是大剂量组病理评分明显低于AOLT组，且中心点OH、O-2（中心点-）和丙二醛水平也明显低于AOLT组。结论：丙泊酚对肝移植后移植肝损伤的保护作用可能与激活Keap 1-Nrf 2信号通路有关。(C)2015 Elsevier Inc. All rights reserved.
Background: 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.Methods: 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 (center dot OH), superoxide anion (O-2(center dot-)), 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.Results: 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 center dot OH, O-2(center dot-), 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.Conclusions: Protective effects of propofol against liver transplantation-induced graft-liver injury may be related with Keap1-Nrf2 signal pathway activation. (C) 2015 Elsevier Inc. All rights reserved.