Effects of hydrogen on nuclear factorE2-related factor 2/antioxidant response element pathway in lung tissues in septic mice

Abstract

Objective To evaluate the effects of hydrogen (H2) on nuclear factorE2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway in lung tissues in septic mice.Methods Seventy-two male ICR mice,weighing 20-25 g,aged 6 weeks,were randomly divided into 4 groups (n =18 each) using a random number table:sham operation group (group SH),group H2,sepsis group (group S),and sepsis + H2 group (group S + H2).Sepsis was produced by cecal ligation and puncture (CLP).H2 and S + H2 groups inhaled 2％ H2 for 1 h starting from 1 and 6 h after CLP.Six mice in each group were chosen and sacrificed at 7,12 and 24 h after CLP (T1-3).The pulmonary specimens were obtained to determine the expression of Nrf2 and HO-1 protein (by Western blot) and Nrf2 mRNA (by RT-PCR).At 24 h after CLP,the pathological changes of lungs were scored,wet/dry lung weight ratio (W/D ratio) was determined,and the expression of high mobility group box-1 (HMGB-1) in lung tissues was measured (by Western blot).Results Compared with group SH,the pathological scores and W/D ratio were significantly increased,and the expression of Nrf2 protein and mRNA,HO-1 and HMGB1 was up-regulated in S and S + H2 groups,while no significant change was found in the indexes mentioned above in group H2.Compared with group S,the pathological scores and W/D ratio were significantly decreased,the expression of Nrf2 protein and mRNA and HO-1 was up-regulated and HMGB1 expression was down-regulated in group S + H2.Conclusion The mechanism by which H2 reduces acute lung injury in septic mice is related to activation of Nrf2/ARE pathway. Key words: Hydrogen ; Sepsis; NF-E2-related factor 2 ; Response elements