Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Department of Anesthesiology, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia Autonomous Region, China.
J Biochem. 2019 Nov 1;166(5):415-421. doi: 10.1093/jb/mvz054.
Reducing oxidative stress is an effective method to prevent hepatic ischaemia/reperfusion injury (HIRI). This study focuses on the role of propofol on the oxidative stress of hepatic cells and the involved lncRNA-TUG1/Brahma-related gene 1 (Brg1) pathway in HIRI mice. The mouse HIRI model was established and was intraperitoneally injected with propofol postconditioning. Hepatic injury indexes were used to evaluate HIRI. The oxidative stress was indicated by increasing 8-isoprostane concentration. Mouse hepatic cell line AML12 was treated with hypoxia and subsequent reoxygenation (H/R). The targeted regulation of lncRNA-TUG1 on Brg1 was proved by RNA pull-down, RIP (RNA-binding protein immunoprecipitation) and the expression level of Brg1 responds to silencing or overexpression of lncRNA-TUG1. Propofol alleviates HIRI and induces the upregulation of lncRNA-TUG1 in the mouse HIRI model. Propofol increases cell viability and lncRNA-TUG1 expression level in H/R-treated hepatic cells. In H/R plus propofol-treated hepatic cells, lncRNA-TUG1 silencing reduces cell viability and increased oxidative stress. LncRNA-TUG1 interacts with Brg1 protein and keeps its level via inhibiting its degradation. Brg1 overexpression reverses lncRNA-TUG1 induced the reduction of cell viability and the increase in oxidative stress. LncRNA-TUG1 silencing abrogates the protective role of propofol against HIRI in the mouse HIRI model. LncRNA-TUG1 has a targeted regulation of Brg1, and thereby affects the oxidative stress induced by HIRI. This pathway mediates the protective effect of propofol against HIRI of hepatic cell.
降低氧化应激是预防肝缺血/再灌注损伤（HIRI）的有效方法。本研究聚焦于异丙酚对 HIRI 小鼠肝细胞氧化应激及涉及的长链非编码 RNA-TUG1/BRG1 相关基因 1（Brg1）通路的作用。建立小鼠 HIRI 模型，并在模型建立后给予异丙酚预处理。采用肝损伤指标评估 HIRI 程度，通过检测 8-异前列腺素浓度来指示氧化应激水平。利用缺氧及随后复氧（H/R）处理小鼠肝星形细胞 AML12 来模拟体内 HIRI 损伤。通过 RNA 下拉实验、RIP（RNA 结合蛋白免疫沉淀）实验证实了 lncRNA-TUG1 对 Brg1 的靶向调控作用，并通过检测 Brg1 表达水平来证实其对 lncRNA-TUG1 沉默或过表达的响应。异丙酚减轻 HIRI 并诱导小鼠 HIRI 模型中 lncRNA-TUG1 的上调。异丙酚增加 H/R 处理的肝细胞中的细胞活力和 lncRNA-TUG1 表达水平。在 H/R 联合异丙酚处理的肝细胞中，沉默 lncRNA-TUG1 降低细胞活力并增加氧化应激。lncRNA-TUG1 与 Brg1 蛋白相互作用并通过抑制其降解来维持其水平。过表达 Brg1 逆转了 lncRNA-TUG1 诱导的细胞活力降低和氧化应激增加。lncRNA-TUG1 沉默消除了异丙酚对小鼠 HIRI 模型中 HIRI 的保护作用。lncRNA-TUG1 对 Brg1 具有靶向调控作用，从而影响 HIRI 诱导的氧化应激。该通路介导了异丙酚对 HIRI 相关的肝细胞保护作用。
