期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 71, 期 -, 页码 52-60出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2019.03.003
关键词
Methane, postoperative cognitive dysfunction; IL-10; Neuro-inflammation; LPS
资金
- National Natural Science Foundation of China [81701062, 81350001, 8177080004]
- Natural Science Foundation of Shanghai [11JC1415500]
- National Key Clinical Project for Army subject Construction
- Scientific Research Foundation of Shanghai Municipal Commission of Health and Family planning [201740050]
Postoperative cognitive dysfunction (POCD) is one of the most common complications after surgery. Accumulating evidence suggests that postoperative neuro-inflammation plays a critical role in the mechanism of POCD. Recently, exogenous methane is reported to have anti-inflammatory properties and play a neuro-protective role in acute carbon monoxide poisoning injury. Therefore, we investigated the protective effect of methane on a POCD model induced by abdominal surgery and its underlying mechanism in aged mice. Methane-rich saline (MS) or normal saline (NS) (16 ml/kg) was injected intraperitoneally 30 min after the abdominal surgery. The result showed that methane attenuated spatial memory loss in Morris water maze (MWM) with decreasing pro-inflammatory cytokines production and activation of microglia in hippocampus after surgery. Meanwhile, methane treatment suppressed lipopolysaccharide (LPS)-stimulated phosphorylation of MAPKs pathways and its downstream target TNF-alpha and IL-6 in BV2 cells. Moreover, methane increased expression of IL-10 in the hippocampus 24 h after surgery, and blockade of IL-10 repressed the protective effect of methane on the cognitive impairments observed in MWM test, decreased microglial activation and the pro-inflammatory cytokine in plasma and hippocampal. Blockade of IL-10 abrogated the suppression effect of methane on the proinflammatory cytokine production and phosphorylation of NF-kappa B and p38MAPK both in hippocampus and in BV2 cells. In conclusion, our study suggests exogenous methane could be a novel agent for the therapy of POCD through its anti-inflammation properties.
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