title: The role of spleen in vagus nerve stimulation for treatment against septic shock in rats.
abstract: OBJECTIVE
  To investigate the role of spleen in vagus nerve stimulation for treatment against septic shock in rats and its underlying mechanism.
  
  
  METHODS
  Sixty-four male Sprague-Dawley (SD) rats were randomly divided into eight groups (n = 8 in each group): sham group, model group, vagotomy group, vagus nerve stimulation group, splenectomy group, splenectomy and vagus nerve stimulation group, common celiac branch vagotomy group, and selective subdiaphragmatic ventral vagotomy group. The septic shock model was reproduced by cecal ligation and puncture (CLP). All the animals were subjected to left cervical vagus nerve isolation or vagotomy, splenectomy was done 3 days before CLP, common celiac branch vagotomy and selective subdiaphragmatic ventral vagotomy were performed after CLP. Mean arterial pressure (MAP) was continuously monitored. Blood was collected 4 hours after CLP for arterial blood gas analysis. The concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) in plasma and spleen were measured by enzyme-linked immunosorbent assay (ELISA). The spleen mRNA expressions of TNF-α and IL-1 were determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Compared with sham group, MAP continuously declined, and lactic acid accumulation and metabolic acidosis appeared in model group, and the contents of TNF-α and IL-1 in plasma and spleen, and mRNA expression of TNF-α and IL-1 in spleen were significantly increased in model group C plasma TNF-α (ng/L) 113.24 5.69 vs. 24. 69 2.56, plasma IL-1 (ng/L) 226.33±9. 12 vs. 34. 58 ± 3.45; spleen TNF-α (ng/g) 286. 1216. 66 vs. 41. 33 2. 35, spleen TNF-a mRNA 1. 12+0.08 vs. 0.22± 0. 02, spleen IL-1 (ng/g) 447. 34 ± 12. 36 vs. 42. 95 ± 2. 33, spleen IL-1 mRNA 0. 93 ± 0. 06 vs. 0. 28 ± 0. 02, all P<0. 013. Compared with model group, lowering of MAP was retarded, lactic acid value and the negative value of base excess (BE) were significantly decreased, the contents of TNF-α and IL-1 in plasma and spleen, and mRNA expression of TNF-α and IL-1 in spleen Uplasma TNF-α (ng/L) 41.00 ± 3.22, plasma IL-1 (ng/L) 63.29±2. 56; spleen TNF-α (ng/g) 74. 22-3.12, spleen TNF-α mRNA 0. 32± 0. 03, spleen IL-1 (ng/g) 81. 54- 5. 48, spleen IL-1 mRNA 0. 35+0.03] were also significantly decreased in vagus nerve stimulation group (P<0. 05 or P<0. 01). However, vagus nerve stimulation after splenectomy failed to show the similar effect as seen in the vagus nerve stimulation group. Compared with vagus nerve stimulation group, the contents of TNF-a and IL-1 in plasma and spleen, and mRNA expression of TNF-α and IL-1 in spleen Eplasma TNF-a (ng/L) 118.38±8. 52, plasma IL-1 (ng/L) 252. 23 9. 55; spleen TNF-α (ng/g) 297.88± 5.44, spleen TNF-a mRNA 0. 68+0. 04, spleen IL-1 (ng/g) 450. 26 12. 45, spleen IL-1 mRNA 0. 96±0. 063 were significantly increased in common celiac branch vagotomy group (P<0. 05 or P< 0. 01). In the selective subdiaphragmatic ventral vagotomy group similar effect with that of the vagus nerve stimulation group was found.
  
  
  CONCLUSIONS
  Vagus nerve stimulation fails to protect against septic shock in rats subjected to splenectomy or common celiac branch vagotomy, indicating that the spleen may be a vital target of the cholinergic anti-inflammatory pathway which is functionally linking with the spleen via the common celiac branch of vagus nerve.
authors.affiliation: Intensive Care Unit, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China.
authors.forename: Na
authors.initials: N
authors.lastname: Xue
authors.forename: Hui
authors.initials: H
authors.lastname: Liang
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.forename: Xue-min
authors.initials: XM
authors.lastname: Song
authors.forename: Jian-guo
authors.initials: JG
authors.lastname: Li
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D007375:Interleukin-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000378:metabolism / Q000517:prevention & control*; D013154:Spleen / Q000378:metabolism*; D013156:Splenectomy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014630:Vagus Nerve / Q000378:metabolism; D055536:Vagus Nerve Stimulation
chemical_list: D007375:Interleukin-1; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D000109:Acetylcholine