大鼠舌鳞癌诱变过程中MMP-3、TIMP-1的表达变化及相关性研究

目的:研究基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶组织抑制因子-1(TIMP-1)在大鼠舌鳞癌诱变过程中转录水平表达变化及两者之间的相关性。方法:60只SD大鼠随机分为3组,每组20只,正常对照组,给予正常饮食;另2组每天喂养0.002%4-硝基喹啉-1-氧化物(4NQO),于16周和24周处死;16周组可见上皮异常增生,而24周组已经为舌鳞癌,分别选取8个标本作检测。各组利用定量逆转录聚合酶链反应(qRT-PCR)检测MMP-3、TIMP-1在不同病变时期舌组织中转录水平的表达变化。结果:MMP-3及TIMP-1的mRNA于正常对照组相对表达量较少,上皮异常增生组相对表达量较正常组显著增加,舌鳞癌组的相对表达量最高。MMP-3与TIMP-1的mRNA表达之间成显著相关性。结论:MMP-3与TIMP-1随癌变的发生表达显著上调,两者间平衡失调可导致舌鳞癌的发生及发展。

Analysis of Matrix Metalloproteinase 3 and Tissue Inhibitors of Matrix Metalloproteinase 1 in Tongue Squamous Cell Carcinoma Rat Model

Objective: To investigate the change and analysis the alteration of matrix metalloproteinase 3(MMP-3) and tissue inhibitors of matrix metalloproteinase 1(TIMP-1).Methods: 60 SD rats randomly divided into three groups.Group 1 and group 2 were given 4-nitroquinoline-1-oxide(4NQO) everyday.Group 3 drank normal saline everyday.Group 1 rats were sacrificed at 16 weeks.Group 2 rats were killed at 24 weeks.Ten rats of control group were killed at 16 weeks and others were killed at 24 weeks.Each sample was divided into two parts.One was underwent histological examination.The other was assayed the kinetics of MMP-3 mRNA and TIMP-1 mRNA expression.Results: Tumors were originated on rats of group given 4NQO at 24 weeks.No tumor originating was found in rats of group given normal saline.The mRNA expression of MMP-3 was increased high in the rats which were caught tongue epithelial dysplasia or tongue squamous cell carcinoma.Moreover,the rats with tongue squamous cell carcinoma showed a higher overregulated expression of MMP-3 than the rats only with tongue epithelial dysplasia.The mRNA expression of TIMP-1 was also overregulated in rats with disease compared to the normal rats.The related relationship of the mRNA expression for MMP-3 and TIMP-1 was significant from the normal rat to the rat with tongue squamous cell carcinoma.Conclusion: The significant imbalance of MMP-3 and TIMP-1 can lead to the occurrence and development of the tongue squamous cell carcinoma.