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目的:评价大鼠肺缺血再灌注时核因子E2相关因子2(Nrf2)与铁死亡的关系。方法:健康雄性SD大鼠54只,体重220~250 g,采用随机数字表法分为3组(n n=18):假手术组(Sham组)、肺缺血再灌注组(IR组)和肺缺血再灌注+Nrf2激动剂萝卜硫素组(IR+SFP组)。采用夹闭左肺门60 min再灌注120 min的方法建立肺缺血再灌注损伤模型。IR+SFP组于肺缺血前3 d腹腔注射萝卜硫素500 μg/kg,1次/d,给药结束后2 h制备模型。再灌注结束时处死大鼠,收集支气管肺泡灌洗液(BALF),BCA法检测蛋白浓度,酶联免疫吸附法测定IL-6、TNF-α浓度;处死后,取肺组织,透射电镜下观察肺组织超微结构,计算肺组织湿重/干重(W/D)比值,比色法检测Fen 2+、MDA、谷胱甘肽(GSH)含量,Western blot法检测核蛋白Nrf2、谷胱甘肽过氧化物酶4(GPX4)、酰基辅酶A合成酶长链家族成员4(ACSL4)表达。n 结果:与Sham组比较,IR组BALF蛋白、IL-6和TNF-α浓度、肺组织W/D比值、Fen 2+和MDA含量升高,GSH含量降低,GPX4表达下调,核蛋白Nrf2、ACSL4表达上调(n P<0.05),Ⅱ型肺泡上皮细胞表现出铁死亡特征性改变包括线粒体皱缩,线粒体嵴减少;与IR组比较,IR+SFP组BALF蛋白、IL-6和TNF-α浓度、肺组织W/D比值、Fen 2+和MDA含量降低,GSH含量升高,核蛋白Nrf2和GPX4表达上调,ACSL4表达下调(n P<0.05),肺组织病理改变明显减轻。n 结论:大鼠肺缺血再灌注时Nrf2可抑制铁死亡,参与其内源性保护机制。“,”Objective:To evaluate the relationship between nuclear factor E2-related factor 2 (Nrf2) and ferroptosis during lung ischemia-reperfusion (I/R) in rats.Methods:Fifty-four healthy male Sprague-Dawley rats, weighing 220-250 g, were divided into 3 groups (n n=18 each) using a random number table method: sham operation group (Sham group), lung I/R group (IR group), and lung I/R+ Nrf2 agonist sulforaphane group (IR+ SFP group). Lung I/R model was developed by clamping the left pulmonary hilum for 60 min followed by 120 min of reperfusion.In IR+ SFP group, SFP 500 μg/kg was intraperitoneally injected at 3 days before lung ischemia once a day for 3 consecutive days, and the model was developed at 2 h after the end of administration.The rats were sacrificed at the end of reperfusion, and the bronchoalveolar lavage fluid (BALF) was collected to determine the protein concentration (using bicinchoninic acid method), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations (by enzyme-linked immunosorbent assay). The animals were then sacrificed, and lung tissue specimens were harvested for microscopic examination of the pathological changes (with a transmission electron microscope) and for determination of wet/dry weight (W/D) ratio, contents of iron, malondialdehyde (MDA) and glutathione (GSH) (by chemical colorimetric) and expression of nuclear Nrf2, glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) (by Western blot).n Results:Compared with Sham group, the concentrations of protein, IL-6 and TNF-α in BALF, W/D ratio, and contents of Fen 2+ and MDA were significantly increased, GSH content was decreased, GPX4 expression was down-regulated, the expression of nuclear Nrf2and ACSL4 was up-regulated (n P<0.05), and the mitochondrial morphology of type Ⅱalveolar epithelial cells showed the characteristic changes of ferroptosis, including the presence of smaller mitochondria and reduced cristae in IR group.Compared with IR group, the concentrations of protein, IL-6 and TNF-α in BALF, W/D ratio, and contents of Fen 2+ and MDA were significantly decreased, GSH content was increased, the expression of nuclear Nrf2 and GPX4 expression was up-regulated, ACSL4 expression was down-regulated (n P<0.05), and the pathological changes of lung tissues were significantly attenuated in IR+ SFP group.n Conclusions:Nrf2 can inhibit ferroptosis during lung I/R and is involved in the endogenous protective mechanism in rats.