Effect of Bowel Resection On Tlr Signaling During Intestinal Adaptation in a Rat Model

Bassel Haj1, Ibrahim Matter1, Yulia Pollak2, Tatiana Dorfman2, Jacob Bejar3, Igor Sukhotnik4. 1Dept of Surgery, 2The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 3Dept of Pathology, 4Dept of Pediatric Surgery, Bnai Zion Medical Center, Haifa, Israel

INTRODUCTION- Bacterial overgrowth is common complication of short bowel syndrome (SBS) and is a result of an impaired gut barrier function.Toll-like receptor 4 (TLR-4) is crucial in maintaining intestinal epithelial homeostasis, participates in a vigorous signaling process and heightens inflammatory cytokine output.The objective of this study was to determine the effects of bowel resection on TLR-4 signaling in intestinal mucosa in a rat model.

METHODS AND PROCEDURES- Male Sprague-Dawley rats were randomly assigned to one of two experimental groups of 8 rats each: Sham rats underwent bowel transection and re-anastomosis, SBS- rats underwent 75% small bowel resection. Rats were sacrificed on day 14. Bacterial translocation (BT) to mesenteric lymph nodes, liver, portal blood and peripheral blood were determined at sacrifice. The expression of TLR-4, MyD88 and TRAF6 in the intestinal mucosa was determined using real time PCR, Western blot and immunohistochemistry.

RESULTS- Sham rats exhibited a 20 % BT to the mesenteric lymph nodes (level I), liver (level II) and blood (level III). SBS rats demonstrated a 100% bacterial translocation (BT) to lymph nodes (Level I) and liver (Level II), and 40% translocation to peripheral blood (Level III). SBS rats have shown a significant increase in TLR-4 mRNA levels in jejunum (60%, p<0.05) as well as in in TLR-4 (three-fold increase, p=0.01) and MyD88 (43%, p<0.05)mRNA levels in ileum compared to control animals. The number of TRAF-6 positive cells (immunohistochemistry) was significantly higher in resected rats compared to sham animals.

CONCLUSION(S)- In a rat model of SBS, elevated intestinal bacterial translocation is associated with a stimulated TLR-4 signaling.

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