Experimental colonic obstruction increases collagen degradation by matrix metalloproteinases in the bowel wall.
OBJECTIVE
Emergency resections for colonic obstruction are accompanied with increased risk of anastomotic dehiscence. Elevated local degradation of submucosal collagens by matrix metalloproteinases may predispose to anastomotic leakage. This study was designed to study the effect of colon obstruction and surgical trauma on matrix metalloproteinase activities and correlate these results to collagen concentration in the colon wall.


METHODS
Colonic obstruction was induced in male, Sprague-Dawley rats (n = 58) by applying a constricting silicone ring around the left colon 3 cm above the peritoneal reflection. After four days of obstruction, 2-mm wide colonic segments were resected approximately 3 mm proximal and 3 mm distal to the stenosis for biochemical analyses. Colonic segments at corresponding locations were obtained from sham-operated rats (n = 5) without obstruction but with silicone ring placed adjacent to colon and from normal, nontraumatized rats (n = 10). Matrix metalloproteinase activity was determined by liberation of fragmented collagens from homogenized colonic tissue incubated ex vivo. Matrix metalloproteinase-2 specifically was analyzed by gelatin zymography.


RESULTS
Endogenous collagenolysis by matrix metalloproteinases increased (P < 0.001) in colon as a consequence of obstruction (4.1-fold) and trauma (1.7-fold) compared with normal colon. In the proximity of the colon stenosis, total matrix metalloproteinase activity and matrix metalloproteinase-2 were significantly (P < 0.05) higher above than below the obstruction. Total activity was 22.9 (13.1-32.9) units/mg collagen proximal and 16.6 (12.7-18.4) units/mg collagen distal to the stenosis. Collagen concentration correlated inversely (r = -0.76; P < 0.001) with total matrix metalloproteinase activity.


CONCLUSIONS
Colonic obstruction and trauma up-regulated matrix metalloproteinases and decreased collagen concentration in colonic wall.
Syk
Ingvar
I
Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
Mirastschijski
Ursula
U
Jeppsson
Bengt W
BW
Agren
Magnus S
MS
D000818:Animals; D003094:Collagen / Q000378:metabolism*; D003106:Colon / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D006909:Hydroxyproline / Q000032:analysis; D007415:Intestinal Obstruction / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D023421:Models, Animal; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D003094:Collagen; D009195:Peroxidase; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D006909:Hydroxyproline