Effect of hydrogen inhalation on brain injury in septic mice / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of hydrogen (H2) inhalation on brain injury in septic mice.Methods One hundred and eighty male ICR mice,aged 6-8 weeks,weighing 20-25 g,were randomly divided into 4 groups (n =45 each) using a random number tablesham operation group (SH group),H2 group,sepsis group (S group) and sepsis + H2 group (S + H2 group).Sepsis was produced by cecal ligation and puncture (CLP) in chloral hydrate-anesthetized mice.H2 and S + H2 groups inhaled 2％ H2 for 1 h starting from 1 and 6 h after CLP.At 7,12 and 24 h after CLP,6 mice in each group were sacrificed and brains were removed for determination of Evans Blue (EB) and water contents in brain tissues.Another 6 mice in each group were chosen at 7,12 and 24 h after CLP,blood samples were obtained,the mice were then sacrificed and brains were removed to measure the concentrations of tumor necrosis factor-α (TNF-α),high mobility group protein B1 (HMGB1) and interleukin-10 (IL-10) in serum and brain tissues by ELISA.Three mice in each group were sacrificed at 24 h after LPS and brains were removed for microscopic examination of pathological changes in hippocampal CA1 region.Six mice in each group were sacrificed at 24 h after LPS and brains were removed for determination of the expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in brain tissues by Western blot.Results Compared with SH group,the contents of EB and water in brain tissues were significantly increased,and the levels of TNF-α,HMGB1 and IL-10 in serum and brain tissues were increased at 7,12 and 24 h after CLP,and the expression of Nrf2 and HO-1 in brain tissues was up-regulated at 24 h after CLP in S and CLP + H2 groups,and no significant difference was found in the index above in H2 group.Compared with S group,the contents of EB and water in brain tissues were significantly decreased,the levels of TNF-α and HMGB1 in serum and brain tissues were decreased and the level of IL-10 in serum and brain tissues was increased at 7,12 and 24 h after CLP,and the expression of Nrf2 and HO-1 in brain tissues was up-regulated at 24 h after CLP and the pathological changes were attenuated in group CLP + H2.Conclusion H2 inhalation can attenuate brain injury in septic mice and the mechanism is related to activation of Nrf2/ARE signaling pathway and inhibition of inflammatory responses.