核因子E2相关因子2激动剂对肺缺血再灌注损伤大鼠的保护作用  

Protective effect of nuclear factor erythroid 2-related factor 2 agonist on lung ischemia-reperfusion injury in rats

作　　者：张建新[1] 马尚超 宋浩 殷飞 Zhang Jianxin;Ma Shangchao;Song Hao;Yin Fei(Department of Critical Care Medicine,the First Afiliated Hospital of Xinxiang Medical University,Weihui 453100,China)

机构地区：[1]新乡医学院第一附属医院重症医学科,卫辉453100

出　　处：《中华实验外科杂志》2024年第3期511-514,共4页Chinese Journal of Experimental Surgery

摘　　要：目的探讨核因子E2相关因子2(Nrf2)激动剂对肺缺血再灌注损伤大鼠的保护作用。方法30只SD大鼠按照随机数字表法分为对照组、再灌注组和Nrf2激动剂组,每组10只。再灌注组和Nrf2激动剂组大鼠采用在体左肺门夹闭法复制缺血再灌注损伤模型,对照组仅作切口,不夹闭。Nrf2激动剂组大鼠建模成功后每天口服富马酸二甲酯100 mg/kg,对照组和再灌注组大鼠每天给予等体积生理盐水。治疗7 d后,取左肺测定组织干湿比和总肺含水量;苏木精-伊红(HE)染色分析大鼠肺泡损伤状况;测定3组大鼠肺组织铁离子、丙二醛(MDA)和谷胱甘肽氧化酶的水平;采用酶联免疫吸附实验分析3组大鼠肺组织炎性因子[肿瘤坏死因子(TNF)、白细胞介素(IL)-6和IL-1β]的水平;蛋白质免疫印迹分析大鼠肺组织铁死亡相关蛋白[转铁蛋白受体1、谷胱甘肽过氧化物酶4(GPX4)和溶质载体家族7成员11]蛋白表达水平。组间计量数据比较采用单因素方差分析。结果Nrf2激动剂组大鼠肺泡损伤百分比[(31.20±5.37)%]明显低于再灌注组[(65.34±5.60)%],差异有统计学意义(t=13.920,P<0.05)。Nrf2激动剂组大鼠肺干湿比(2.44±0.13)明显低于再灌注组(3.85±0.39),差异有统计学意义(t=10.950,P<0.05)。Nrf2激动剂组大鼠血清TNF、IL-6和IL-1β[(33.44±4.72)、(27.61±1.73)、(23.87±2.64)pg/ml]明显低于再灌注组[(78.85±9.63)、(43.12±10.46)、(39.79±8.78)pg/ml],差异有统计学意义(t=13.390、4.625、5.488,P<0.05)。Nrf2激动剂组大鼠肺组织铁离子浓度[(0.62±0.12)μmol/mg]明显低于再灌注组[(1.01±0.10)μmol/mg],差异有统计学意义(t=7.823,P<0.05)。Nrf2激动剂组大鼠肺组织MDA水平[(1.06±0.07)μmol/mg]明显低于再灌注组[(1.68±0.14)μmol/mg],差异有统计学意义(t=12.370,P<0.05)。Nrf2激动剂组大鼠谷胱甘肽过氧化物酶(GSH-Px)活性[(137.70±11.27)U/mg]明显低于再灌注组[(102.90±10.48)U/mg],差异有统计学意义(t=7.148,P<0.05)�Objective To investigate the protective effect of nuclear factor erythroid 2-related factor 2(Nrf2)agonist on lung ischemia-reperfusion injury in rats.MethodsTotally,30 SD rats were divided into control group,reperfusion group and Nrf2 agonist group with 10 rats in each group according to the random number table method.The rats in the reperfusion group and the Nrf2 agonist group were subjected to the left hilar clamp method to replicate the ischemia-reperfusion injury model,while the control group was subjected to incision without clamp.After successful modeling,rats in the Nrf2 agonist group were given dimethyl fumarate 100 mg/kg orally every day,and those in the control group and reperfusion group were given equal volume of normal saline every day.After 7 days of treatment,the dry-wet ratio and total lung water content were measured in the left lung.Hematoxylin and eosin(HE)staining was used to analyze the alveolar damage in rats.The levels of iron ion,malondialdehyde(MDA)and glutathione oxidase in lung tissues were determined.The levels of lung inflammatory factors[tumor necrosis factor(TNF),interleukin(IL)-6 and IL-1β]were analyzed by enzyme-linked immunosorbent assay(ELISA).The expression levels of iron death-related proteins(transferrin receptor 1,glutathione peroxidase 4 and solsolic carrier family 7 members 11)in rat lung tissues were analyzed by Western blotting.One-way analysis of variance was used to compare the measurement data between groups.ResultsThe percentage of alveolar damage in the Nrf2 agonist group[(31.20±5.37)%]was significantly lower than that in the reperfusion group[(65.34±5.60)%,t=13.920,P<0.05].The dry/wet lung ratio in the Nrf2 agonist group(2.44±0.13)was significantly lower than that in the reperfusion group(3.85±0.39,t=10.950,P<0.05).Serum TNF,IL-6 and IL-1βlevels in the Nrf2 agonist group[(33.44±4.72),(27.61±1.73),(23.87±2.64)pg/ml]were lower than those in the reperfusion group[(78.85±9.63),(43.12±10.46),(39.79±8.78)pg/ml,t=13.390,4.625,5.488,P<0.05].The concentration o

关 键 词：核因子E2相关因子2激动剂 肺缺血再灌注损伤 富马酸二甲酯 炎性因子 铁死亡 

分 类 号：R563[医药卫生—呼吸系统]