Role of nuclear factor erythroid 2-related factor in hydrogen-induced reduction of intestinal injury in mice with sepsis / 中华麻醉学杂志

ABSTRACT

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 tablesham 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 intestinai tissues were removed for determination of the tumor necrosis factor-alpha (TNF-α),interleukin-1beta (IL-1β) and high-mobility group box 1 protein (HMGB 1) 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 micecompared 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).For wild type micecompared with group Sep,the levels of TNF-α,IL-1β,MDA and 8-iso-PGF2α were significantly decreased,the expression of HMGB1 protein and mRNA was down-regulated,the expression of HO-1 protein and mRNA was upregulated,and the activities of CAT and SOD were increased in group H2 (P＜0.05).For Nrf2 gene knockout miceno significant difference was found in the parameters mentioned above between group H2 and 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.