title: The role of spleen in the treatment of experimental lipopolysaccharide-induced sepsis with dexmedetomidine.
abstract: Dexmedetomidine (Dex), a highly selective α2-adrenergic receptor agonist, has been shown to attenuate systemic inflammatory response induced by lipopolysaccharide (LPS). The protective effects of Dex may reportedly be due to the activation of the α7 nicotinic acetylcholine receptor (α7nAChR)-dependent cholinergic anti-inflammatory pathway. Spleen has been shown to play a pivotal role in the neural cholinergic anti-inflammatory pathway. However, little is known about the specific function of spleen in the protective effects of Dex against sepsis. To investigate the role of spleen in the treatment of Dex against sepsis, we studied the effects of preemptive administration of Dex to septic mice on the NF-κB p65 activation and downstream pro-inflammatory cytokine expression in the spleen. Our results provided evidence that Dex treatment attenuated LPS-activated NF-κB p65 activation, as well as the production of tumor necrosis factor-α, interleukin-6, and interleukin-1β at the level of both mRNA and protein in spleen. Consequently, serum concentrations of these cytokines decreased. Conversely, preemptive injection of α-bungarotoxin, a selective α7nAChR antagonist, reversed these effects of Dex. Our findings indicated that spleen played a critical role in the protective effects of Dex against sepsis and provided further insight into the anti-inflammatory mechanisms of Dex.
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, Binzhou, 256603 Shandong People's Republic of China.
authors.forename: Zhaoguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, Binzhou, 256603 Shandong People's Republic of China.
authors.forename: Yaoqi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, Binzhou, 256603 Shandong People's Republic of China.
authors.forename: Qiaoqing
authors.initials: Q
authors.lastname: Ning
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, Binzhou, 256603 Shandong People's Republic of China.
authors.forename: Chunzhi
authors.initials: C
authors.lastname: Gong
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, Binzhou, 256603 Shandong People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, Binzhou, 256603 Shandong People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, Binzhou, 256603 Shandong People's Republic of China.
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Bu
authors.affiliation: Department of Anesthesiology, Binzhou Medical University Hospital, Binzhou, 256603 Shandong People's Republic of China.
authors.forename: Guangjian
authors.initials: G
authors.lastname: Jing
keywords: Cholinergic anti-inflammatory pathway; Dexmedetomidine; Lipopolysaccharides; Sepsis; Spleen