THE PROTECTIVE EFFECT OF THE CHOLINERGIC ANTI-INFLAMMATORY PATHWAY AGAINST SEPTIC SHOCK IN RATS


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Abstract

To investigate the effects of the cholinergic anti-inflammatory pathway on hemodynamics, blood biochemistry, the plasma TNF-α level, and the nuclear factor-κB (NF-κB) 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 α-BGT group was administered α-bungarotoxin before electrical stimulation of the vagus nerve. The right carotid artery was cannulated to monitor MAP. The plasma TNF-α level was measured using enzyme-linked immunosorbent assays. The hepatic NF-κB 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-α level and the hepatic NF-κB 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-α production, but electrical stimulation had no effect on the hepatic NF-κB activation. Tetrahydroaminoacridine administration after bilateral cervical vagotomy reversed hypotension and attenuated the plasma TNF-α response; in addition, it had no effect on the hepatic NF-κB activation. α-Bungarotoxin pretreatment significantly reversed the inhibitory effect of vagal electrical stimulation, but it had no effect on the hepatic NF-κB activation. Our results showed that the cholinergic anti-inflammatory pathway might produce a potential protective effect on polymicrobial sepsis in rats.

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