Hypothermic oxygenated perfusion ameliorates ischemia- reperfusion injury of fatty liver in mice via Brg1/ Nrf2/HO-1 axis
Hypothermic oxygenated perfusion ameliorates ischemia- reperfusion injury of fatty liver in mice via Brg1/ Nrf2/HO-1 axis
复制标题
低温氧合灌注通过Brg1/Nrf2/HO-1轴改善小鼠脂肪肝缺血再灌注损伤
DOI：
10.1111/aor.14076
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发表时间：
--
影响因子：
2.4
通讯作者：
Fan Xiaoli
中科院分区：
文献类型：
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作者：
Wang Shengjie;Zeng Xianpeng;Yang Yunying;Li Shiyi;Wang Yanfeng;Ye Qifa;Fan Xiaoli
研究背景脂肪肝在冷保存及移植后较健康肝更易发生肝功能障碍和严重的术后并发症。低温充氧灌注（HOPE）是一种安全有效的系统，可修复脂肪肝，减轻缺血再灌注损伤。本研究旨在探讨Brg 1/Nrf 2/HO-1信号通路在HOPE对脂肪肝缺血再灌注损伤保护作用中的作用。将动物分为对照组、CS组和HOPE组。采用肝酶和乳酸水平检测肝脏功能和细胞代谢。HE染色观察组织结构变化，TUNEL染色观察细胞凋亡情况。检测肝组织超氧化物歧化酶（SOD）、丙二醛（MDA）和活性氧（ROS）水平，定量分析氧化应激程度;采用Western blot方法检测Brg 1、Nrf 2和HO-1蛋白表达。免疫荧光双标记法检测Brg 1和Nrf 2的共定位。结果CS组肝脏损伤较对照组严重。而HOPE能明显减轻损伤，表现为肝功能和细胞代谢的改善，细胞凋亡、坏死和氧化应激程度的降低。HOPE组Brg 1、Nrf 2和HO-1的表达较CS组明显增加。结论HOPE预处理1 h可明显改善小鼠脂肪肝再灌注损伤。其机制可能是Brg 1和Nrf 2的相互作用选择性地激活HO-1的转录。
BackgroundAfter cold storage (CS) and subsequent transplantation, fatty liver is more inclined to develop liver dysfunction and serious postoperative complications in contrast to healthy liver. Hypothermic oxygenated perfusion (HOPE) is a safe and efficacious system, which can repair fatty liver and reduce ischemia‐reperfusion injury. The aim of this research is to investigate the function of Brg1/Nrf2/HO‐1 signaling pathway in the protective effect of HOPE on ischemia‐reperfusion injury of fatty liver.MethodsThe mouse fatty liver model was successfully established and verified by hematoxylin‐eosin (HE) staining and oil red O staining. The animals were divided into Control group, CS group and HOPE group. The levels of liver enzyme and lactate in the perfusate were used to measure liver function and cellular metabolism. HE staining and TUNEL staining were utilized to assess the tissue structure and apoptosis, respectively. The levels of superoxide dismutase, malondialdehyde and reactive oxygen species in liver tissue were measured to quantitatively analyze the degree of oxidative stress, and the expressions of protein Brg1, Nrf2 and HO‐1 were detected by means of the western blot. Double‐labeling immunofluorescence was to explore the colocalization of Brg1 and Nrf2.ResultsThe injury of the liver in the CS group was more serious than that in the control group. However, HOPE could significantly reduce the injury, which was manifested by the improvement of liver function and cellular metabolism, and the lower degrees of apoptosis, necrosis and oxidative stress. Furthermore, the expressions of Brg1, Nrf2 and HO‐1 in the HOPE group were significantly increased than those in the CS group.ConclusionsOne‐hour HOPE treatment before reperfusion can obviously improve the injury of fatty liver in mice. The underlying mechanism may be that the interaction of Brg1 and Nrf2 can selectively activate the transcription of HO‐1.