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基质金属蛋白酶-2,9及其抑制剂与大肠腺瘤癌变的关系 被引量:2

Roles of MMP-2, MMP-9 and their inhibitors in progression of colorectal neoplasm into colorectal carcinoma
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摘要 目的:探讨基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制剂-2(TIMP-2)、基质金属蛋白酶抑制剂-1(TIMP-1)在不同性质的大肠黏膜中的表达情况及MMP-2/TIMP-2、MMP-9/ TIMP-1与大肠腺瘤向大肠癌转变的相关性及临床意义. 方法:用酶联免疫吸附试验(ELISA)的方法对MMP-2, MMP-9及其抑制剂TIMP-2、TIMP-1在大肠腺瘤轻、中、重度不典型增生以及大肠腺癌中进行定量检测. 结果:MMP-2在大肠腺瘤重度不典型增生与中含量明显高于轻、中度不典型增生及正常大肠黏膜(91.391±23.551 vs 19.461±8.836,42.313±14.094,27.330±8.405,P<0.05);MMP-9在正常肠黏膜中未见表达, 在大肠腺瘤轻中重度不典型增生及大肠癌中表达依次增强,两两间有显著性差异(11.260±4.104 vs 31.520±7,433 vs 57.803±19.060 vs 202.17±33.344,P<0.05); TIMP-2重度不典型增生组与正常大肠黏膜有显著性差异(136.279±19.539 vs 81.363±26.252,P<0.05); MMP-2/TIMP-2比率在腺瘤轻、中度不典型增生, 重度不典型增生及大肠腺癌中两两之间均有显著性差异(0.206±0.128 vs 0.360±0.129 vs 0.665±0.100 vs 1.136±0.300,P<0.05);TIMP-1在腺瘤轻中度不典型增生中表达与大肠腺癌中表达有显著性差异(227.413±208.497,654.854±339.005 vs 1136.271±607.029 P<0.05); MMP-9/TIMP-1比率在腺瘤轻中度不典型增生,重度不典型增生及大肠腺癌中两两之间均无显著性差异(P>0.05). 结论:MMP-2可能是大肠腺瘤向大肠腺癌转变过程中的早期事件.MMP-9可作为区别大肠肿瘤良恶性的一项重要指标.MMP-2/TIMP-2比率与大肠腺瘤恶变有相关性,而MMP-9/TIMP-1的比率与大肠腺瘤向大肠腺癌的转变无相关性.MMP-2、MMP-9的定量监测可以作为大肠腺瘤向大肠腺癌转变过程中重要的生物学指标. AIM: To investigate the expression of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-2 (TIMP-2) and TIMP-1 colorectal mucous tissues with different types, and to explore the clinical significance of MMP-2/TIMP-2, MMP-9/TIMP-1 in the progression of colorectal neoplasm into colorectal carcinoma. METHODS: The expression of MMP-2, MMP-9 and their inhibitors TIMP-2, TIMP-1 were detected in the mild, moderate and severe dysplasia of colorectal neoplasm and colorectal carcinoma by enzyme linked immunosorbent assay (ELISA). RESULTS: The expression of MMP-2 in the severe dysplasia of colorectal neoplasm significantly higher than that in the mild and moderate ones and normal mucosa (91.391±23.551 vs 19.461±8.836, 42.313±14.094, 27.330±8.405, P<0.05). MMP-9 was not expressed in normal colorectal mucosa, but its expression was successively in mild (11.260±4.104), moderate (31.520±7.433) and severe (57.803±19.060) dysplasia as well as in colorectal carcinoma (202.17±33.344). Marked difference was detected between any two of them (P<0.05). TIMP-2 was differently expressed between severe dysplasia and normal colorectal mucosa (136.279±19.539 vs 81.363±26.252, P<0.05). The ratio of MMP-2 to TIMP-2 was significantly different between mild, moderate and severe dysplasia and colorectal carcinoma (0.206±0.128 vs 0.360±0.129 vs 0.665±0.100 vs 1.136±0.300, P<0.05). TIMP-1 expression was obviously decreased in mild and medium dysplasia as compared with that in colorectal carcinoma (227.413±208.497, 654.854±339.005 vs 1136.271±607.029, P<0.05).The ratio of MMP-9 to TIMP-1 showed no marked difference between mild, moderate and severe dysplasia and colorectal carcinoma (P>0.05). CONCLUSION: MMP-2 may be an important marker in the progression of colorectal neoplasm into colorectal carcinoma. MMP-9 can be applied to differentiate benign tumors from malignant ones. The ratio of MMP-2 to TIMP-2 is associated with colorectal neoplasm's progression into carcinoma, but the ratio of MMP-9 to TIMP-1 isn't. MMP-2 and MMP-9 may be used as valuable biological markers for predicting progression of colorectal neoplasm into carcinoma.
出处 《世界华人消化杂志》 CAS 北大核心 2005年第13期1514-1518,共5页 World Chinese Journal of Digestology
基金 黑龙江省科技厅攻关课题 No.GB01C12403~~
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参考文献28

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