摘要
目的探讨核因子E2相关因子2(Nrf2)信号通路通过缺血后处理激活对肺缺血再灌注损伤的保护作用及机制.方法 30只无特定病原体动物(SPF)级SD大鼠随机分为3组(n=10):缺血再灌注损伤(IRI)手术处理组、Sham假手术组及缺血后处理组.建立肺脏缺血再灌注损伤大鼠模型及缺血后处理大鼠模型,缺血后处理组建模后进行缺血后处理,Sham假手术组除不用无损伤动脉夹钳夹左侧肺脏外,其他一切步骤与缺血再灌注手术组相同.应用SPSS 18.0统计软件分析,计数资料行x2检验,采用n(%)表示,计量资料行t检验,采用均值±标准差(Mean±SD)表示.结果缺血后处理组肺脏体重、湿/干重比(W/D)水平,均低于IRI手术处理组及Sham假手术组(P<0.05);IRI手术处理组肺脏体重、W/D水平,均低于Sham假手术组(P<0.05);Sham假手术组在不阻断肺门持续灌注105 min后,肺泡壁薄,结构清晰,无明显水肿,近似正常肺组织结构;IRI手术处理组缺血45 min再灌注60 min后,肺泡间隔明显增宽,肺水肿明显,肺泡腔内浆液渗出;IPC缺血后处理组再灌注前给予10 min后处理后,肺泡间隔变窄,水肿减轻.缺血后处理组Nrf2、皮质过氧化物酶6(Prx6)、血红素加氧酶-1(HO-1)、依赖还原型辅酶Ⅰ/Ⅱ醌氧化还原酶(NQO1)、谷氨酸半胱胺酸连接酶修饰亚基(Gclm) RNA水平,均低于IRI手术处理组和Sham组(P<0.05).结论 SD大鼠中Nrf2能通过Nrf2-ARE信号能调控氧化应激损伤,经过缺血后处理后能通过Nrf2抵抗氧化应激损伤.
Objective To investigate the protective effect and mechanism of nuclear factor E2 related factor 2 (Nrf2) signaling pathway on lung ischemia-reperfusion injury (IRI) through ischemic postconditioning. Methods Thirty non-specific pathogen (SPF) SD rats were randomly divided into 3 groups (n=10 each group): IRI surgical treatment group, sham operation group and ischemic post-treatment group. Rat model of lung IRI and rat model of ischemic postconditioning were established. The ischemic post-treatment group was modeled for ischemic postconditioning. In the sham operation group, except for the left lung without clamping artery, the rest procedures were the same as in the IRI surgical treatment group. Results The body weight and wet/dry weight ratio (W/D) in the ischemic post-treatment group were significantly lower than those in the IRI surgical treatment group and the sham operation group (P<0.05). The lung weight and W/D level in the IRI surgical treatment group were significantly lower than in the sham operation group (P<0.05). The sham operation group had a thin alveolar wall and clear structure without obvious edema after 105 min of continuous perfusion of the hilar, similar to normal lung tissue structure. In IRI surgical treatment (45 min of ischemia and 60 min of reperfusion), the alveolar space was significantly widened, the pulmonary edema was significantly aggravated, and the pulp in the alveolar cavity was exuded. In the ischemic post-treatment group, the alveolar space became narrower and the edema was relieved. Thee mRNA expression levels of Nrf2, corticoperoxidase 6 (Prx6), heme oxygenase-1 (HO-1), coenzyme Ⅰ/Ⅱ oxidoreductase (NQO1), glutamate caspase and amino acid ligase modified subunit (Gclm) in the ischemic post-treatment group were significantly reduced as compared with those in the IRI surgical treatment group and sham operation group (all P<0.05). Conclusion Nrf2 can regulate oxidative stress injury through Nrf2-ARE signaling in SD rats, and it can resist oxidative stress damage through Nrf2 after ischemic postconditioning.
作者
王继武
陈小珍
徐志强
胡赞歌
李鸣
Wang Jiwu;Chen Xiaozhen;Xu Zhiqiang;Hu Zange;Li Ming(Pu’ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430034, China)
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2019年第8期1430-1432,共3页
Chinese Journal of Experimental Surgery
基金
2018年湖北省知识创新专项(自然科学基金)项目(2018CFB736).
关键词
核因子E2相关因子2信号通路
缺血后处理
肺缺血再灌注损伤
保护作用
Nuclear factor E2 related factor 2 signaling pathway
Ischemic postconditioning
Lung ischemia-reperfusion injury
Protective effect
