| First Author | Yang J | Year | 2013 |
| Journal | Surgery | Volume | 153 |
| Issue | 1 | Pages | 52-62 |
| PubMed ID | 22703966 | Mgi Jnum | J:314778 |
| Mgi Id | MGI:6822366 | Doi | 10.1016/j.surg.2012.04.002 |
| Citation | Yang J, et al. (2013) Heparin-binding epidermal growth factor-like growth factor improves intestinal barrier function and reduces mortality in a murine model of peritonitis. Surgery 153(1):52-62 |
| abstractText | BACKGROUND: The morbidity and mortality associated with bacterial peritonitis remain high. Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a potent intestinal cytoprotective agent. The aim of this study was to evaluate the effect of HB-EGF in a model of murine peritonitis. METHODS: HB-EGF(-/-) knockout (KO) mice and their HB-EGF(+/+) wild-type (WT) counterparts were subjected to sham operation, cecal ligation and puncture (CLP), or CLP with HB-EGF treatment (800 mug/kg IP daily). Villous length, intestinal permeability, intestinal epithelial cell (IEC) apoptosis, bacterial load in peritoneal fluid (PF) and mesenteric lymph nodes (MLN), inflammatory cytokine levels, and survival were determined. RESULTS: After exposure to CLP, HB-EGF KO mice had significantly shorter villi (1.37 +/- 0.13 vs 1.96 +/- 0.4 relative units; P < .03), increased intestinal permeability (17.01 +/- 5.18 vs 11.50 +/- 4.67 nL/min/cm2; P < .03), increased IEC apoptotic indices (0.0093 +/- 0.0033 vs 0.0016 +/- 0.0014; P < .01), and increased bacterial counts in PF (25,313 +/- 17,558 vs 11,955 +/- 6,653 colony forming units [CFU]/mL; P < .05) and MLN (19,009 +/- 11,200 vs 5,948 +/- 2,988 CFU/mL/g; P < .01) compared with WT mice. Administration of HB-EGF to WT and HB-EGF KO mice exposed to CLP led to significantly increased villous length and decreased intestinal permeability, IEC apoptosis and bacterial counts in MLN (P < .05). Survival of HB-EGF KO mice subjected to CLP was significantly improved with administration of HB-EGF (P < .05). CONCLUSION: HB-EGF gene KO increases susceptibility to peritonitis-induced intestinal injury, which can be reversed by administration of HB-EGF. These results support a protective role of HB-EGF in peritonitis-induced sepsis. |
