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目的 探讨基质金属蛋白酶 9(MMP 9) /金属蛋白酶组织抑制物 1(TIMP 1)系统在IgA肾病肾组织中的表达及其对IgA肾病的进展的影响。方法 采用免疫组织化学和原位杂交技术 ,分别在蛋白质和基因水平检测 38例IgA肾病患者肾组织中的MMP 9和TIMP 1的变化。结果 MMP 9在正常肾脏肾小球的脏层上皮细胞和内皮细胞有少量表达 ,在肾小管上皮细胞和间质血管壁也有少量表达 ;在IgA肾病中 ,MMP 9在系膜增殖性肾小球和间质血管壁的表达均明显增多 (P <0 0 0 1) ,而在硬化肾小球内的表达则明显减少 ,肾小管细胞的MMP 9表达无明显变化。TIMP 1在正常肾组织中不能检出 ,在IgA肾病患者具有系膜增殖性病变的肾小球中有微量表达 ,在增殖很重但尚未完全硬化的肾小球内表达增多 ,在肾小管间质表达最为明显 (P <0 0 0 1) ,其主要见于肾小管细胞、间质细胞和血管内皮细胞。肾组织中的TIMP 1表达与血清肌酐水平呈显著相关 (P <0 0 5 ) ,与肾小管间质的纤维化和炎细胞浸润程度亦明显相关 (P值均 <0 0 1)。肾小球中的MMP 9表达与尿蛋白无明显相关性 ,但与血清肌酐水平呈显著负相关 (P <0 0 5 )。结论 MMP 9和TIMP 1的异常表达可能是影响IgA肾病进展的因素之一
Objective To investigate the expression of matrix metalloproteinase 9 (MMP 9) / tissue inhibitor of metalloproteinase 1 (TIMP 1) in IgA nephropathy and its effect on progression of IgA nephropathy. Methods Immunohistochemistry and in situ hybridization were used to detect the changes of MMP 9 and TIMP-1 in renal tissues of 38 patients with IgA nephropathy at the protein and gene level respectively. Results MMP 9 was slightly expressed in the visceral epithelial cells and endothelial cells of normal kidney glomeruli, with a slight expression in renal tubular epithelial cells and interstitial blood vessel walls. In IgA nephropathy, MMP 9 was expressed in mesangial proliferative glomeruli And interstitial vessel wall (P <0.01), while the expression in sclerotic glomeruli was significantly reduced, and the expression of MMP 9 in tubular cells did not change significantly. TIMP-1 can not be detected in normal kidney tissue, it has a slight expression in glomerular mesangial proliferative glomerulonephritis patients with IgA nephropathy, increased expression in glomeruli which proliferate but not yet fully sclerosis, The most significant expression (P <0.01), which is mainly found in tubular cells, stromal cells and vascular endothelial cells. The expression of TIMP-1 in renal tissue was significantly correlated with serum creatinine (P <0.05), and also with the degree of tubulointerstitial fibrosis and inflammatory cell infiltration (P <0.01). There was no significant correlation between the expression of MMP 9 and urinary protein in glomeruli, but negatively correlated with serum creatinine (P <0.05). Conclusion The abnormal expression of MMP-9 and TIMP-1 may be one of the factors affecting the progression of IgA nephropathy