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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.
RESUMO
Objective To observe the effects of acupuncture on TLR4, inflammation factors IL-1β and IL-6 expressions in the prefrontal cortex of vascular dementia (VD) rats; To investigate the brain protective mechanisms of acupuncture. Methods A total of 50 rats were randomly divided into sham-operation group, model group, acupuncture group, and placebo-acupuncture group. The animal model of VD was replicated by permanent bilateral common carotid artery occlusion (2VO) in rats. Acupuncture was performed at three days after surgery, once daily for two weeks. Morris water maze was used to test the cognitive function. The expressions of Iba1 and TLR4 were assessed by immunohistochemical method. Inflammation factors IL-1β and IL-6 mRNA expressions were tested by RT-PCR. Results Compared with sham-operation group, the model group rats showed impaired spatial learning and memory ability, and expression of Iba1, TLR4, and IL-1β, IL-6 increased. Compared with the model group, the spatial learning and memory abilities of the acupuncture group were improved, and the expression of Iba1, TLR4 and IL-1β, IL-6 in the prefrontal cortex decreased. These effects were not found in the placebo-acupuncture group. Conclusion The effect of acupuncture may be achieved by inhibiting microglia activate, decreasing the expressions of TLR4, IL-1β and IL-6 in the prefrontal cortex, resulting in improving spatial learning and memory ability of VD rats.