Gut mucosal injury is attenuated by recombinant bactericidal/permeability-increasing protein in hind limb ischemia-reperfusion injury.
Lower limb ischemia-reperfusion injury (IRI) is associated with increased gut permeability to endotoxin, which not only directly damages enterocytes but also stimulates a systemic inflammatory response syndrome (SIRS), compounding gut injury. Recombinant bactericidal/permeability-increasing protein (rBPI21) is a novel anti-endotoxin therapy with proven benefit in sepsis. Its potential role in modulating remote gut injury in hind limb IRI was studied. Male Wistar rats were chosen for a prospective randomized control trial (n = 10 per group). The control group and two groups undergoing 3 hr bilateral hind limb ischemia with 2 hr reperfusion (I/R) were randomized to receive intravenously either control protein thaumatin at 2 mg/kg or rBPI21 at 2 mg/kg, respectively. Quantitative morphometric assessment of the small bowel was used as a measure of gut injury and, using an ex vivo everted gut sac model, translocation of 14C-labeled polyethylene glycol (PEG) was used as a measure of gut permeability. Our results indicate that hind limb IRI is associated with remote gut mucosal injury and increased permeability to macromolecules. rBPI21 anti-endotoxin therapy modulates remote gut injury associated with lower limb IRI in this model.
Harkin
D W
DW
Department of Surgery, Queen's University of Belfast, Institute of Clinical Sciences, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland.
D'Sa
A A
AA
Yassin
M M
MM
Hoper
M
M
Halliday
M I
MI
D000818:Animals; D004731:Endotoxins / Q000627:therapeutic use*; D007421:Intestine, Small / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy*
D004731:Endotoxins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C025357:endotoxin binding proteins