Syk Ingvar, Mirastschijski Ursula, Jeppsson Bengt W, Agren Magnus S
Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
Dis Colon Rectum. 2003 Sep;46(9):1251-9. doi: 10.1007/s10350-004-6723-x.
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.
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.
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.
Colonic obstruction and trauma up-regulated matrix metalloproteinases and decreased collagen concentration in colonic wall.
结肠梗阻急诊切除术后吻合口裂开风险增加。基质金属蛋白酶导致的黏膜下胶原蛋白局部降解增加可能易引发吻合口漏。本研究旨在探讨结肠梗阻和手术创伤对基质金属蛋白酶活性的影响，并将这些结果与结肠壁中的胶原蛋白浓度相关联。
在雄性Sprague-Dawley大鼠（n = 58）中，通过在腹膜反折上方3 cm处的左结肠周围应用缩窄硅胶环诱导结肠梗阻。梗阻4天后，切除狭窄部位近端约3 mm和远端约3 mm处2 mm宽的结肠段进行生化分析。从假手术大鼠（n = 5）获取相应位置的结肠段，这些大鼠未发生梗阻，但硅胶环置于结肠旁，同时从正常、未受创伤的大鼠（n = 10）获取结肠段。通过体外孵育匀浆结肠组织释放片段化胶原蛋白来测定基质金属蛋白酶活性。采用明胶酶谱法专门分析基质金属蛋白酶-2。
与正常结肠相比，由于梗阻（4.1倍）和创伤（1.7倍），结肠中基质金属蛋白酶引起的内源性胶原分解增加（P < 0.001）。在结肠狭窄附近，梗阻上方的总基质金属蛋白酶活性和基质金属蛋白酶-2显著高于下方（P < 0.05）。狭窄近端总活性为22.9（13.1 - 32.9）单位/毫克胶原蛋白，远端为16.6（12.7 - 18.4）单位/毫克胶原蛋白。胶原蛋白浓度与总基质金属蛋白酶活性呈负相关（r = -0.76；P < 0.001）。
结肠梗阻和创伤上调了基质金属蛋白酶并降低了结肠壁中的胶原蛋白浓度。
