Mechanism underlyinghydrogen-induced reduction of sepsis-associated encephalopathy in mice:phenotypic transformation of hippocampal microglias / 中华麻醉学杂志

ABSTRACT

Objective To investigate the relationship between the mechanism underlying hydrogeninduced reduction of sepsis-associated encephalopathy (SAE) and phenotypic transformation of hippocampal microglias in mice.Methods Eighty-eight adult male ICR mice,aged 6-8 weeks,weighing 20-25 g,were divided into 4 groups (n =22 each) using a random number table method:sham operation group (group Sham),sham operation plus hydrogen group (group Sham+H2),SAE group and SAE plus hydrogen group (group SAE + H2).Sepsis was induced by cecal ligation and puncture (CLP) in anesthetized mice.Sham and Sham+H2 groups only underwent simple laparotomy.Sham+H2 and SAE+H2 groups inhaled air containing 2％ hydrogen for 1 h starting from 1 and 6 h after CLP,respectively.Mice were sacrificed at 24 h after CLP,and hippocampi were isolated for determination of the levels of tumor necrosis factor (TNF-α),interleukin-6 (IL-6),transforming growth factor-β (TGF-β) and IL-10 (by enzyme-linked immunosorbent assay) and expression of inducible nitric oxide synthase (iNOS) and argininase-1 (Arg-1) (by Western blot).Morris water maze test was performed on 10 mice in each group at days 4-8 after CLP.PResults Compared with group Sham,the levels of TNF-α,IL-6,TGF-β and IL-10 were significantly increased,the expression of iNOS and Arg-1 was up-regulated,the escape latency was prolonged,and the rate of time spent in the target quadrant and the number of crossing the original platform were reduced in SAE and SAE+H2 groups (P＜0.05).Compared with group SAE,the levels of TNF-α and IL-6 were significantly decreased,the expression of iNOS was down-regulated,the expression of TGF-β,IL-10 and Arg-1 was up-regulated,the escape latency was shortened,and the rate of time spent in the target quadrant and the number of crossing the original platform were increased in group SAE+H2 (P＜0.05).Conclusion Hydrogen can promote phenotypic transformation of hippocampal microglias from M1 to M2 and reduce SAE in mice.