Ge Mian, Luo Gangjian, Yao Weifeng, Luo Chenfang, Zhou Shaoli, Yuan Dongdong, Chi Xinjin, Hei Ziqing
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China.
Mol Med Rep. 2015 May;11(5):3962-8. doi: 10.3892/mmr.2014.3126. Epub 2014 Dec 22.
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 (O2•‑), 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, O2•‑ and ·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.
核因子红细胞2相关因子2（Nrf2）是细胞防御反应中抵御氧化损伤的关键调节因子。多项研究表明，丙泊酚可改善多种器官的缺血/再灌注损伤。然而，丙泊酚是否通过激活Nrf2对肝移植发挥肾脏保护作用仍有待阐明。本研究的目的是探讨原位肝自体移植（OLAT）对肾脏Nrf2表达的影响，并确定丙泊酚是否通过激活Nrf2来保护免受OLAT诱导的肾损伤。将24只雄性Sprague Dawley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+丙泊酚50 mg/kg（L-丙泊酚组）和OLAT+丙泊酚100 mg/kg（H-丙泊酚组）。在手术前通过腹腔注射连续3天给予生理盐水和丙泊酚。在OLAT后8小时评估肾脏病理学、血尿素氮（BUN）、肌酐（Cr）、超氧阴离子（O2•-）、羟自由基（·OH）、丙二醛（MDA）以及Nrf2、 Kelch样ECH相关蛋白1（Keap1）、血红素加氧酶-1（HO-1）和NADP醌氧化还原酶1（NQO1）的表达水平。结果表明，OLAT诱导了远隔肾损伤。丙泊酚预处理显著改善了肾脏病理学，并消除了OLAT诱导的Cr和BUN浓度、O2•-和·OH活性以及MDA水平的升高。在H-丙泊酚组中，细胞质中Keap1表达降低，细胞核中Nrf2表达上调，同时伴有HO-1和NQO1表达增加。本研究结果表明，丙泊酚预处理对OLAT发挥了肾脏保护作用，核Nrf2表达上调可能是其潜在机制。
