title: The protective effect of the cholinergic anti-inflammatory pathway against septic shock in rats.
abstract: To investigate the effects of the cholinergic anti-inflammatory pathway on hemodynamics, blood biochemistry, the plasma TNF-alpha level, and the nuclear factor-kappaB (NF-kappaB) activation during septic shock, male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP, a model of polymicrobial sepsis) or sham operation. Forty-eight rats were randomly assigned into six equal groups: sham CLP group; CLP group; VGX group was subjected to bilateral cervical vagotomy after CLP; STM group was subjected to bilateral cervical vagotomy after CLP plus the left vagus nerve trunk electrical stimulation; THA group was administered tetrahydroaminoacridine after CLP and bilateral cervical vagotomy; and alpha-BGT group was administered alpha-bungarotoxin before electrical stimulation of the vagus nerve. The right carotid artery was cannulated to monitor MAP. The plasma TNF-alpha level was measured using enzyme-linked immunosorbent assays. The hepatic NF-kappaB activation was determined by Western blotting. Cecal ligation and puncture produced progressive hypotension. Serum aspartate transaminase and alanine transaminase levels significantly increased after CLP challenge. The plasma TNF-alpha level and the hepatic NF-kappaB activation significantly increased after CLP alone or with bilateral cervical vagotomy compared with sham-operated group. Application of constant voltage pulses to the caudal vagus trunk significantly prevented the development of CLP-induced hypotension, alleviated the hepatic damage, and reduced the plasma TNF-alpha production, but electrical stimulation had no effect on the hepatic NF-kappaB activation. Tetrahydroaminoacridine administration after bilateral cervical vagotomy reversed hypotension and attenuated the plasma TNF-alpha response; in addition, it had no effect on the hepatic NF-kappaB activation. alpha-Bungarotoxin pretreatment significantly reversed the inhibitory effect of vagal electrical stimulation, but it had no effect on the hepatic NF-kappaB activation. Our results showed that the cholinergic anti-inflammatory pathway might produce a potential protective effect on polymicrobial sepsis in rats.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Zhongnan Hospital, Wuhan University, Wuhan, Hubei Province, China.
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Song
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Li
authors.forename: Yan-Lin
authors.initials: YL
authors.lastname: Wang
authors.forename: Zheng-Fang
authors.initials: ZF
authors.lastname: Hu
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Du
authors.forename: Bao-Hui
authors.initials: BH
authors.lastname: Jia
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004558:Electric Stimulation; D007249:Inflammation; D008099:Liver / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012772:Shock, Septic / Q000628:therapy*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014630:Vagus Nerve / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D011950:Receptors, Cholinergic; D014409:Tumor Necrosis Factor-alpha