Protective mechanism of nuclear factor E2 related factor 2 signaling pathway on lung ischemia-reperfusion injury

Abstract

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. Key words: Nuclear factor E2 related factor 2 signaling pathway; Ischemic postconditioning; Lung ischemia-reperfusion injury; Protective effect