title: Dexmedetomidine attenuates inflammatory reaction in the lung tissues of septic mice by activating cholinergic anti-inflammatory pathway.
abstract: Dexmedetomidine (Dex) is a highly selective α2-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-κB p65 activity. The production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) at both the mRNA and protein levels was also reduced. Moreover, these effects were significantly blocked by the α7 nicotinic acetylcholine receptor (α7nAChR) antagonist α-bungarotoxin (α-Bgt). α-Bgt aggravated pulmonary edema and pulmonary histopathological changes, as well as increased NF-κB p65 activity and TNF-α 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 α7nAChR-dependent cholinergic anti-inflammatory pathway.
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, No. 661, Huanghe 2nd Road, Binzhou 256603, Shandong, China.
authors.forename: Zhaoguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, No. 661, Huanghe 2nd Road, Binzhou 256603, Shandong, China.
authors.forename: Yueping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, No. 661, Huanghe 2nd Road, Binzhou 256603, Shandong, China. Electronic address: wangyaoqi2006@163.com.
authors.forename: Yaoqi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, No. 661, Huanghe 2nd Road, Binzhou 256603, Shandong, China.
authors.forename: Qiaoqing
authors.initials: Q
authors.lastname: Ning
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, No. 661, Huanghe 2nd Road, Binzhou 256603, Shandong, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, No. 661, Huanghe 2nd Road, Binzhou 256603, Shandong, China.
authors.forename: Chunzhi
authors.initials: C
authors.lastname: Gong
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, No. 661, Huanghe 2nd Road, Binzhou 256603, Shandong, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, No. 661, Huanghe 2nd Road, Binzhou 256603, Shandong, China.
authors.forename: Guangjian
authors.initials: G
authors.lastname: Jing
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, No. 661, Huanghe 2nd Road, Binzhou 256603, Shandong, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Wang
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002038:Bungarotoxins / Q000008:administration & dosage / Q000494:pharmacology; D020927:Dexmedetomidine / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D011014:Pneumonia / Q000188:drug therapy*; D018805:Sepsis / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000893:Anti-Inflammatory Agents; D002038:Bungarotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D064569:alpha7 Nicotinic Acetylcholine Receptor; D020927:Dexmedetomidine
keywords: Cholinergic anti-inflammatory pathway; Dexmedetomidine; Lipopolysaccharides; Lung; Sepsis