Objective To evaluate the role of nuclear factor erythroid 2-related factor (Nrf2) in hydrogen-induced reduction of intestinal injury in mice with sepsis. Methods Eighteen pathogen-free male wild type mice and 18 male Nrf2 gene knockout mice, aged 6-8 weeks, weighing 20-25 g, were studied.The mice of either type were assigned into 3 groups (n=6 each) using a random number table: sham operation group (group Sham), sepsis group (group Sep) and hydrogen group (group H2). Sepsis was induced by cecal ligation and puncture in chloral hydrate-anesthetized mice.The mice inhaled 2% hydrogen for 1 h starting from 1 and 6 h after operation in group H2.The mice were sacrificed at 24 h after operation, and small intestinal tissues were removed for determination of the tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and high-mobility group box 1 protein (HMGB1) contents (by enzyme-linked immunosorbent assay), superoxide dismutase (SOD) and catalase (CAT) activities and malondialdehyde (MDA) content (using a spectrophotometer), 8-iso-prostaglandin F2α (8-iso-PGF2α) content (with Multiskan Spectrum plate reader), and expression of heme oxygenase-1 (HO-1) and HMGB1 protein and mRNA (by Western blot or real-time polymerase chain reaction). Results For wild type and Nrf2 gene knockout mice: compared with group Sham, the contents of TNF-α, IL-1β, HMGB1, MDA and 8-iso-PGF2α were significantly increased, the expression of HO-1 and HMGB1 protein and mRNA was up-regulated, and the activities of CAT and SOD were decreased in group Sep (P 0.05). Compared with group H2 of wild type mice, the levels of TNF-α, IL-1β, MDA and 8-iso-PGF2α were significantly increased, the expression of HMGB1 protein and mRNA was up-regulated, the expression of HO-1 protein and mRNA was down-regulated, and the activities of CAT and SOD were decreased in group H2 of Nrf2 gene knockout mice (P<0.05). Conclusion The mechanism by which hydrogen reduces the intestinal injury is related to Nrf2 in mice with sepsis. Key words: NF-E2-related factor 2; Mice, knockout; Hydrogen; Sepsis; Intestinal injury
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