Journal of Gastrointestinal Surgery

, Volume 13, Issue 5, pp 983–993 | Cite as

Somatostatin Limits Intestinal Ischemia-Reperfusion Injury in Macaques via Suppression of TLR4-NF-κB Cytokine Pathway

  • Hao Wu
  • Ling Liu
  • Qinghua Tan
  • Chunhui Wang
  • Meimei Guo
  • Yongmei Xie
  • Chengwei Tang
Original Article

Abstract

Objective

Intestinal ischemia-reperfusion (IIR)-induced gut injury remains a challenge for critically ill patients despite the oxidative stress theory that has been elaborated. This study aimed to test whether Toll-like receptor 4 (TLR4) is involved in gut injury during IIR and whether somatostatin (SST) affects TLR4-nuclear factor-κB (NF-κB) cytokine pathway in the intestinal mucosa of macaques.

Design

Fifteen macaques were randomized into control, IIR, and SST + IIR groups. Pieces of isolated ileal epithelium from each animal were incubated with lipopolysaccharide (LPS), interferon-γ, or SST. Expression of TLR4 and NF-κBp65 was evaluated by immunohistochemical staining, Western blot analysis and reverse transcription polymerase chain reaction. Cytokine levels were measured by ELISA. Radioimmunoassay was used to determine of SST levels.

Measurements and Main Results

Significant overexpression (IIR vs control) of ileal TLR4 (0.17 ± 0.03 vs 0.05 ± 0.02), NF-κBp65 (0.55 ± 0.11 vs 0.15 ± 0.05), and TNF-α (213.2 ± 29.2 vs 56.0 ± 10.04) after IIR was greatly decreased (p < 0.05) by prophylactic use of SST (TLR4: 0.06 ± 0.02; NF-κBp65: 0.26 ± 0.09; TNF-α: 97.1 ± 32.3) in vivo. TLR4 expression in the ileal epithelium treated with LPS and SST (1,330 ± 93) was significantly lower than that in the ileal epithelium treated with LPS alone (2,088 ± 126) in vitro. SST levels in plasma (3.67 ± 0.41 ng/ml) and ileal mucosa (1,402.3 ± 160 ng/mg protein) of the IIR group were significantly lower than those (6.09 ± 1.29 ng/ml, 2,234. 8 ± 301.8 ng/mg protein) in the control group (p < 0.05).

Conclusions

Endogenous SST is a crucial inhibitor of massive inflammatory injury in the intestinal mucosa via direct suppression of the TLR4-NF-κB cytokine pathway induced by LPS in ileal epithelium. IIR attacks caused shortages of endogenous SST in the plasma and intestinal mucosa of macaques in this study. Therefore, preventive supplements of SST may limit intestinal injury of macaques by IIR.

Keywords

Somatostatin (SST) Toll-like receptor 4 (TLR4) NF-κB Intestinal ischemia-reperfusion (IIR) Macaques Cytokine 

Notes

Acknowledgment

This work was performed at the Laboratory of Peptides Related to Human Diseases, West China Hospital, Sichuan University and was supported by the technicians in that laboratory.

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Copyright information

© The Society for Surgery of the Alimentary Tract 2009

Authors and Affiliations

  • Hao Wu
    • 1
  • Ling Liu
    • 2
  • Qinghua Tan
    • 2
  • Chunhui Wang
    • 1
  • Meimei Guo
    • 2
  • Yongmei Xie
    • 2
  • Chengwei Tang
    • 1
  1. 1.Department of Gastroenterology, West China HospitalSichuan UniversityChengduPeople’s Republic of China
  2. 2.Lab. Peptides Related to Human Diseases, West China HospitalSichuan UniversityChengduPeople’s Republic of China

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