Propofol pretreatment attenuates remote kidney injury induced by orthotopic liver autotransplantation, which is correlated with the activation of Nrf2 in rats
Propofol pretreatment attenuates remote kidney injury induced by orthotopic liver autotransplantation, which is correlated with the activation of Nrf2 in rats
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DOI：
10.3892/mmr.2014.3126
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发表时间：
2015-05-01
影响因子：
3.4
通讯作者：
Hei, Ziqing
中科院分区：
文献类型：
--
作者：
Ge, Mian;Luo, Gangjian;Hei, Ziqing
核因子红细胞2相关因子2（Nrf 2）是细胞防御反应的关键调节因子，可保护细胞免受氧化损伤。几项研究表明，丙泊酚可改善许多器官的缺血/再灌注损伤。然而，丙泊酚是否通过激活Nrf 2对肝移植产生肾保护作用仍有待阐明。本研究的目的是研究原位肝自体移植（OLAT）对肾脏Nrf 2表达的影响，并确定丙泊酚是否通过激活Nrf 2来保护OLAT诱导的肾损伤。将24只雄性Sprague道利大鼠随机分为四组：假手术+生理盐水（假手术组）; OLAT +生理盐水（OLAT组）; OLAT +异丙酚50 mg/kg（L-Prop组）和OLAT +异丙酚100 mg/kg（H-Prop组）。手术前连续3天腹腔注射生理盐水和丙泊酚。OLAT后8 h观察肾脏病理、血尿素氮（BUN）、肌酐（Cr）、超氧阴离子（O-2（中点-））、羟自由基（OH）、丙二醛（MDA）以及Nrf 2、Kelch样ECH相关蛋白1（Keap 1）、血红素加氧酶-1（HO-1）和NADP奎宁氧化还原酶1（NQO 1）的表达水平。研究表明，OLAT可诱导远端肾损伤。异丙酚预处理可明显改善肾脏病理，并消除OLAT引起的Cr和BUN浓度、O-2（中心点-）和中心点OH活性以及MDA水平的升高。在H-Prop组中，Keap 1在胞浆中的表达减少，Nrf 2在胞核中的表达上调，同时伴有HO-1和NQO 1表达的增加。目前的研究结果表明，异丙酚预处理对OLAT的肾保护作用，核Nrf 2表达上调作为一个潜在的机制。
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical regulator of the cellular-defense response in protection against oxidative injury. Several studies have demonstrated that propofol ameliorates ischemia/reperfusion injury in a number of organs. However, whether propofol exerts renal protection against liver transplantation via Nrf2 activation remains to be elucidated. The aim of the present study was to investigate the effects of orthotopic liver autotransplantation (OLAT) on renal Nrf2 expression and to determine whether propofol protects against kidney injury induced by OLAT via Nrf2 activation. A total of 24 male Sprague Dawley rats were randomly divided into four groups: sham surgery + normal saline (sham group); OLAT + normal saline (OLAT group); OLAT + propofol 50 mg/kg (L-Prop group) and OLAT + propofol 100 mg/kg (H-Prop group). Normal saline and propofol were administered for 3 consecutive days through an intraperitoneal injection prior to surgery. Kidney pathology, blood urea nitrogen (BUN), creatinine (Cr), superoxide anion (O-2(center dot-)), hydroxyl radical (OH), maleic dialdehyde (MDA) and expression levels of Nrf2, Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1) and NADP quinine oxidoreductase 1 (NQO1) were assessed 8 h after OLAT. It was demonstrated that OLAT induced remote kidney damage. Pretreatment with propofol significantly ameliorated renal pathology and abrogated the increase of the Cr and BUN concentrations, O-2(center dot-) and center dot OH activities, and MDA levels induced by OLAT. In the H-Prop group, Keap1 expression in the cytoplasm was decreased and Nrf2 expression in the nucleus was upregulated, accompanied by an increase of HO-1 and NQO1 expression. The present results suggest that propofol pretreatment exerted renal protection against OLAT, with the upregulation of nuclear Nrf2 expression as a potential mechanism.