Yao Weifeng, Luo Gangjian, Zhu Guosong, Chi Xinjin, Zhang Ailan, Xia Zhengyuan, Hei Ziqing
Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, China.
Department of Anesthesiology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450000, China.
Oxid Med Cell Longev. 2014;2014:258567. doi: 10.1155/2014/258567. Epub 2014 Feb 11.
This study aimed to investigate whether propofol pretreatment can protect against liver transplantation-induced acute lung injury (ALI) and to explore whether Nrf2 pathway is involved in the protections provided by propofol pretreatment.
Adult male Sprague-Dawley rats were divided into five groups based on the random number table. Lung pathology was observed by optical microscopy. Lung water content was assessed by wet/dry ratio, and PaO2 was detected by blood gas analysis. The contents of H2O2, MDA, and SOD activity were determined by ELISA method, and the expression of HO-1, NQO1, Keap1, and nuclear Nrf2 was assayed by western blotting.
Compared with saline-treated model group, both propofol and N-acetylcysteine pretreatment can reduce the acute lung injury caused by orthotopic autologous liver transplantation (OALT), decrease the lung injury scores, lung water content, and H2O2 and MDA levels, and improve the arterial PaO2 and SOD activity. Furthermore, propofol (but not N-acetylcysteine) pretreatment especially in high dose inhibited the expression of Keap1 and induced translocation of Nrf2 into the nucleus to further upregulate the expression of HO-1 and NQO1 downstream.
Pretreatment with propofol is associated with attenuation of OALT-induced ALI, and the Nrf2 pathway is involved in the antioxidative processes.
本研究旨在探讨丙泊酚预处理是否能预防肝移植诱导的急性肺损伤（ALI），并探究Nrf2信号通路是否参与丙泊酚预处理提供的保护作用。
成年雄性Sprague-Dawley大鼠根据随机数字表分为五组。通过光学显微镜观察肺组织病理学变化。采用湿/干比评估肺含水量，通过血气分析检测动脉血氧分压（PaO2）。采用酶联免疫吸附测定法（ELISA）测定过氧化氢（H2O2）、丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性，采用蛋白质免疫印迹法检测血红素加氧酶-1（HO-1）、醌氧化还原酶1（NQO1）、 Kelch样环氧氯丙烷相关蛋白1（Keap1）及细胞核Nrf2的表达。
与生理盐水处理的模型组相比，丙泊酚和N-乙酰半胱氨酸预处理均能减轻原位自体肝移植（OALT）引起的急性肺损伤，降低肺损伤评分、肺含水量、H2O2及MDA水平，提高动脉PaO2及SOD活性。此外，丙泊酚（而非N-乙酰半胱氨酸）预处理，尤其是高剂量时，可抑制Keap1的表达，诱导Nrf2向细胞核内转位，进而上调下游HO-1和NQO1的表达。
丙泊酚预处理可减轻OALT诱导的ALI，Nrf2信号通路参与了其抗氧化过程。
