Dexmedetomidine attenuates inflammatory reaction in the lung tissues of septic mice by activating cholinergic anti-inflammatory pathway

摘要

Dexmedetomidine (Dex) is a highly selective alpha 2-adrenergic receptor agonist that is widely used for sedation in intensive care units and in clinical anesthesia. Dex has also been shown to possess anti-inflammatory benefits. However, the underlying mechanism by which Dex relieves the inflammatory reaction in the lung tissues of septic mice has not been fully elucidated. In this study, we aimed to evaluate the protective effects and possible mechanism of Dex on the sepsis-induced lung inflammatory response in mice. Sepsis was induced in mice models through the intraperitoneal injection of lipopolysaccharide (LPS). The preemptive administration of Dex substantially abated sepsis-induced pulmonary edema, pulmonary histopathological changes, and NF-kappa B p65 activity. The production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) at both the mRNA and protein levels was also reduced. Moreover, these effects were significantly blocked by the alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) antagonist a-bungarotoxin (alpha-Bgt). alpha-Bgt aggravated pulmonary edema and pulmonary histopathological changes, as well as increased NF-kappa B p65 activity and TNF-alpha and IL-6 expression at both the mRNA and protein levels. The overall results demonstrate that Dex inhibits the LPS-induced inflammatory reaction in the lung tissues of septic mice partly through the alpha 7nAChR-dependent cholinergic anti-inflammatory pathway. (C) 2016 Elsevier B.V. All rights reserved.