溃疡性结肠炎患者基质金属蛋白酶-2,9和抑制因子-1,2的表达及其意义

Expression and activity analysis of MMP-2,9,TIMP-1,2 in patients with ulcerative colitis

目的 在转录和蛋白水平检测基质金属蛋白酶 (MMP) 2 ,9和特异性组织抑制因子(TIMP) 1,2在溃疡性结肠炎 (UC)患者和正常志愿者肠粘膜中的表达情况及活性变化。方法 对病理证实的 2 2例UC和 2 0名健康志愿者在内窥镜下取活检 ,采用NorthernBlot和WesternBlot法分别对MMP 2 ,9及TIMP 1,2进行检测 ,并采用明胶酶谱法测定MMP 2 ,9活性。结果 MMP 2 ,9和TIMP 1在正常肠粘膜中均呈现低表达 ,在患者肠粘膜中表达显著升高 (P <0 .0 1) ,而TIMP 2在两种粘膜中的表达量无明显差别。明胶酶谱结果显示MMP 2 ,9在后者中的活性较前者中显著升高 (P <0 .0 5 ) ,且与炎症程度相关。结论 MMP 2 ,9在UC肠炎肠粘膜上皮重塑过程中具有重要作用 。

Objective To investigate the expression and enzyme activity of matrix metalloproteinase(MMP) 2,9 and tissue inhibitor of MMP(TIMP) 1,2 in inflamed and uninflamed colonic mucosa in patients with ulcerative colitis(UC).Methods Twenty two patients with UC and 20 healthy controls were employed in this study.Biopsies were taken from inflamed and normal regions and inflammation was graded.The expression levels of MMP 2,9 and TIMP 1,2 were determined by Northern blotting and Western blotting.Gelatinase zymography was also used to assay the activity of MMP 2,9.Results Both TIMP 1 and MMP 2,9 were undetectable in the majority of uninflamed samples from controls.However,they were much higher in those of UC( P <0.01);TIMP 2 level of the colonic mucosa was not different in UC patients and normal controls.Gelatinase zymography shows that the enzyme activity is greatly higher in inflamed mucosa than that of controls,and is consistent with the inflammatory grade.Conclusion MMP 2,9 are involved in mucosal remodeling in UC,which may affect disease development.