Meijer M J W, Mieremet-Ooms M A C, van der Zon A M, van Duijn W, van Hogezand R A, Sier C F M, Hommes D W, Lamers C B H W, Verspaget H W
Department of Gastroenterology-Hepatology, C4P, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Dig Liver Dis. 2007 Aug;39(8):733-9. doi: 10.1016/j.dld.2007.05.010. Epub 2007 Jun 29.
Matrix metalloproteinases are associated with matrix turnover in both physiological and pathological conditions. We postulate an association between aberrant matrix metalloproteinases proteolytic activity and the intestinal tissue destruction, seen in patients with Crohn's disease and/or ulcerative colitis.
Surgically resected inflamed and non-inflamed ileum and colon with/without extensive fibrosis from 122 Crohn's disease, 20 ulcerative colitis and 62 control patients were homogenized. Protein levels of matrix metalloproteinases and tissue inhibitor of metalloproteinases were measured by enzyme-linked immunosorbent assays (ELISA), while matrix metalloproteinases and myeloperoxidase activity were measured by specific activity assays.
Expression of total levels of matrix metalloproteinases-1, -2, -3 and -9 relative to tissue inhibitor of metalloproteinases-1 and -2 was increased in inflamed inflammatory bowel disease compared to non-inflamed inflammatory bowel disease and control intestinal mucosa. Also, net matrix metalloproteinases-1, -2, -3 and -9 activity in inflamed inflammatory bowel disease was increased, with similar expression profiles in Crohn's disease and ulcerative colitis. Within inflamed inflammatory bowel disease, a close correlation of matrix metalloproteinases with myeloperoxidase was observed. The expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases was similar in inflamed Crohn's disease tissue with or without extensive fibrosis and not related to fistulizing disease.
We have shown increased net matrix metalloproteinases activity in intestinal inflammatory bowel disease tissue, likely to contribute to the tissue damage and remodelling seen in inflammatory bowel disease.
基质金属蛋白酶在生理和病理条件下均与基质周转有关。我们推测，在克罗恩病和/或溃疡性结肠炎患者中所见的异常基质金属蛋白酶蛋白水解活性与肠道组织破坏之间存在关联。
将122例克罗恩病患者、20例溃疡性结肠炎患者和62例对照患者手术切除的发炎和未发炎的回肠及结肠（有或无广泛纤维化）进行匀浆处理。通过酶联免疫吸附测定（ELISA）测量基质金属蛋白酶和金属蛋白酶组织抑制剂的蛋白质水平，同时通过比活性测定测量基质金属蛋白酶和髓过氧化物酶活性。
与未发炎的炎症性肠病和对照肠黏膜相比，发炎的炎症性肠病中基质金属蛋白酶-1、-2、-3和-9相对于金属蛋白酶组织抑制剂-1和-2的总水平表达增加。此外，发炎的炎症性肠病中基质金属蛋白酶-1、-2、-3和-9的净活性增加，在克罗恩病和溃疡性结肠炎中的表达谱相似。在发炎的炎症性肠病中，观察到基质金属蛋白酶与髓过氧化物酶密切相关。在有或无广泛纤维化的发炎的克罗恩病组织中，基质金属蛋白酶和金属蛋白酶组织抑制剂的表达相似，且与瘘管形成疾病无关。
我们已证实在肠道炎症性肠病组织中基质金属蛋白酶的净活性增加，这可能导致炎症性肠病中所见的组织损伤和重塑。
