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目的:探究NF-E2相关因子2(Nrf2)在海水淹溺引起的小鼠肺损伤中的作用和意义。方法:48只6~8周龄雄性野生型C57小鼠随机按2批进行实验并分组:(1)对照组、海水淹溺后第1天组(Day1)、第3天组(Day3)和第7天组(Day7),以确定海水淹溺时间点。(2)对照组、海水淹溺模型组(SW)、富马酸二甲酯(DMF)处理组和海水淹溺+DMF处理组(SW+DMF),以验证Nrf2在鼠溺水性肺损伤中的作用。每组6只小鼠。12只6~8周龄雄性C57背景的Nrf2基因敲除小鼠(Nrf2 KO)随机分为Nrf2 KO对照组和Nrf2 KO+海水淹溺组;每组6只小鼠。淹溺造模后3 d取材,观察肺大体形态,观察肺组织病理形态变化,计算肺湿/干质量比,检测还原型谷胱甘肽和丙二醛含量。结果:海水淹溺导致小鼠肺泡腔破坏、肺出血和肺水肿;相比于野生型小鼠,敲除Nrf2加重了海水淹溺引起的小鼠肺损伤和氧化应激;Nrf2激动剂DMF减轻小鼠肺损伤,增加还原型谷胱甘肽含量并且降低丙二醛含量。结论:Nrf2激活能够减轻海水淹溺引起的小鼠肺损伤和氧化应激,在减轻溺水性肺损伤中起重要作用。“,”Objective:To investigate the role of NF-E2-related factor 2 (Nrf2) in lung injury caused by seawater drowning in mice.Methods:A total of 48 6-8 weeks old male wild-type C57 mice were randomly divided into two groups for experiment: (1) control group, day 1 group after drowning(Day1), day 3 group after drowning(Day3) and day 7 group after drowning(Day7) to determine the time point of seawater drowning; (2) control group, seawater drowning model group(SW), dimethyl fumarate treatment group(DMF) and seawater drowning+ DMF reatment group(SW+ DMF) to determine the role of Nrf2 in lung injury in mice caused by drowning, 6 mice per group. And 12 male C57 background Nrf2 knockout mice (Nrf2 KO) at 6-8 weeks old were divided into Nrf2 KO control group and Nrf2 KO+ seawater drowning group; 6 mice in each group. Three days after the drowning model was established, we observed the gross morphology and the pathological changes of the lung tissue, calculated the wet-to-dry weight ratio of the lungs, and tested the reduced glutathione and malondialdehyde levels.Results:Seawater drowning caused alveolar space rupture, pulmonary hemorrhage and pulmonary edema in mice. Compared with the wild-type mice, knockout of Nrf2 aggravated lung injury and oxidative stress in mice caused by seawater drowning. Nrf2 agonist DMF treatment significantly improved lung injury in mice, increased the reduced glutathione content, and decreased malondialdehyde level.Conclusion:The activation of Nrf2 can relieve lung injury and oxidative stress levels in mice caused by seawater drowning, which can play an important role in reducing lung damage caused by seawater drowning.