title: Vagus nerve electrical stimulation inhibits serum levels of S100A8 protein in septic shock rats.
abstract: The vagus nerve and the released acetylcholine exert anti-inflammatory effects and inhibit septic shock. However, their detailed mechanisms remain to be elucidated. The present study aimed to investigate the effects of vagus nerve electrical stimulation on serum S100A8 levels in septic shock rats. A total of 36 male Sprague-Dawley rats were randomly divided into six equal groups: i) Sham group, receiving sham operation; ii) CLP group, subjected to cecal ligation and puncture (CLP) to establish a model of polymicrobial sepsis; iii) VGX group, subjected to CLP and bilateral cervical vagotomy; iv) STM group, subjected to CLP, bilateral cervical vagotomy and electrical stimulation on the left vagus nerve trunk; v) α‑bungarotoxin (BGT) group was administered α‑BGT prior to electrical stimulation; vi) Anti‑receptor for advanced glycation end products (RAGE) group, administered intraperitoneal injection of anti‑RAGE antibody prior to electrical stimulation. The right carotid artery was cannulated to monitor mean artery pressure (MAP). The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to assess the liver function. Serum S100A8 and advanced glycation end product (AGE) levels were measured using enzyme‑linked immunosorbent assays. The expression of hepatic RAGE was determined by western blotting. The present study revealed that Sprague‑Dawley rats exhibited progressive hypotension and significantly increased serum AST and ALT levels following CLP challenge compared with the sham group. The levels of S100A8 and AGEs, and the protein expression of hepatic RAGE were significantly increased following CLP compared with the sham group. Vagus nerve electrical stimulation significantly prevented the development of CLP‑induced hypotension, alleviated the hepatic damage, reduced serum S100A8 and AGEs production, and reduced the expression of hepatic RAGE. The inhibitory effect of vagus nerve electrical stimulation was reversed by pre-treatment with α-BGT and enhanced by pre-treatment with anti-RAGE antibody. In conclusion, vagus nerve electrical stimulation may produce a protective effect on septic shock in rats by decreasing the production of S100A8.
authors.affiliation: Department of Critical Care Medicine, Shanghai Seventh People's Hospital, Shanghai 200137, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.affiliation: Shanghai Institute of Medical Genetics, Shanghai Children's Hospital Affiliated to Shanghai Jiao‑Tong University, Shanghai 200040, P.R. China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Liu
mesh_terms: D000818:Animals; D040501:Calgranulin A / Q000097:blood*; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000097:blood*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000097:blood* / Q000628:therapy; D055536:Vagus Nerve Stimulation
chemical_list: D040501:Calgranulin A; D017127:Glycation End Products, Advanced