人视网膜色素上皮细胞中MMP-2和TIMP-1表达的调节

Regulation of MMP-2 and TIMP-1 Expression in Human RPE Cells

目的 观察转化生长因子β1（TGF-β1）对体外培养的人视网膜色素上皮（retinal pigment epithelium，RPE）细胞中基质金属蛋白酶-2（MMP-2）及其组织型抑制剂（tissue inhibitor of metalloproteinase-1，TIMP-1）表达的调节作用。方法 体外培养的第3～5代人眼RPE细胞经0．00（对照组）、0．01、0．10、1.00及10．00ng／ml TGF-β1处理24h后，采用免疫组织化学方法和计算机图像分析系统检测TGF-β1对体外培养的人RPE细胞MMP-2和TIMP-1表达的影响。结果0．10、1.00及10．00ng／ml TGF-β1处理组MMP-2阳性细胞的平均吸光度（A）值分别为（0．13±0．02）、（0．14±0．01）和（0．18±0．02），与对照组（0．09±0．02）相比差异均有显著性意义（P〈0．05或0．01）；TIMP-1阳性细胞的平均吸光度（A）值，除了0．10ng／ml TGF-β1作用组外，其它浓度TGF-β1作用组与对照组相比差异无显著性意义（均P〉0．05）。结论 人RPE细胞中TGF-β1对上调MMP-2的表达起重要作用，这也是MMP-2／TIMP-1之间平衡改变的原因。

Objective To investigate the modulation of matrix metalloproteinase-2 （MMP-2） and its tissue inhibitor （TIMP-1） by TGF-β1 in human retinal pigment epithelial （RPE） cells. Methods MMP-2 and TIMP-1 expression in cultured 3 -5 passage human RPE cells were detected by immunohistochemistry method, and the results were analyzed by computer medical image analysis system after treated with 0.00 ng/ml （control）, 0.01, 0.10, 1.00 and 10.00 ng/ml TGF-β1 for 24 h. Results The mean A value of MMP-2 positive staining cells treated with 0.10, 1.00 and 10.00 ng/ml TGF-β1 was （0.13±0.02）, （0. 14±0. 01） and （0.18±0.02）, respectively. The difference between these groups and that of the control group （0.09±0.02） was statistically significant （P〈0.05 or 0.01）. Except 0. 10 ng/ml TGF-β1 group, the mean A value of TIMP positive staining cells in other TGF-β1 groups had no significant difference compared with control group （P〉0.05）. Conclusion TGF-β1 may play an important role in the up-regulation of expression of MMP-2 protein in RPE cells and account for a directional shift in the balance between MMP-2 and TIMP-1.