基质金属蛋白酶9、3和金属蛋白酶组织抑制物1在原发性膜性肾病肾小球内的表达及意义

目的探讨基质金属蛋白酶9（MMP-9）、基质金属蛋白酶3（MMP-3）和金属蛋白酶组织抑制物1（TIMP-1）在原发性膜性肾病（IMN）患者肾小球内的表达变化及其与蛋白尿、Scr的关系。方法用免疫组织化学技术分别检测44例IMN患者（IMN组）与6例正常对照者（对照组）肾小球内MMP-9、MMP-3和TIMP-1的表达。结果MMP-9及MMP-3在对照组正常肾组织的肾小管上皮细胞、肾间质和肾小球足细胞有少量表达；在IMN组肾小球足细胞、系膜细胞、肾小球基底膜及肾小管上皮细胞有表达。IMN组肾小球内MMP-9及MMP-3的表达均较对照组显著增强（P〈0．05）。TIMP-1在对照组正常肾组织的肾小管上皮细胞有少量表达，肾小球内无表达；在IMN组肾小球足细胞、肾小管上皮细胞有表达。IMN组肾小球内TIMP-1的表达较对照组显著增强（P〈0．01）。IMN组24h尿蛋白定量显著高于对照组（P〈0．01）。Ⅱ期MN组肾小球MMP-9／TIMP-1及MMP-3／TIMP-1比值较Ⅰ期MN组明显下降（P〈0．01）。IMN组肾小球内MMP-9的表达与Scr呈负相关（r=-0．02，P〈0．05）；TIMP-1的表达与Scr呈正相关（r=0．34，P〈0．05）。结论MMP-9与TIMP-1从正反两方面影响IMN患者肾功能的改变。MMP-9、MMP-3的异常表达与IMN患者蛋白尿之间可能相关；IMN患者肾小球MMP／TIMP比值失衡可能与IMN患者肾小球基底膜增厚相关。

Expression and significance of MMP-9,MMP-3 and TIMP-1 in glomeruli of patients with idiopathic membranous nephropathy

Objective To explore the expression of matrix metalloproteinase-9 (MMP-9), metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinse-1 (TIMP-1) in the glomeruli of patients with idiopathic membranous nephropathy ((?)MN) , and its relationship to albuminuria and serum creatinine. Methods Immunohistochemistry was applied to detect the expression of MMP-9, MMP-3 and TIMP-1 in renal glomerulus of patients with IMN (IMN group) and the control group. Results MMP-9 and MMP-3 were expressed at a low level in tubular epithelial cells, interstitium and podocytes of control group. MMP-9 and MMP-3 were expressed in podocytes, mesangial cells, glomerular basement membrane and tubular epithelial cells of IMN group. The expression of MMP-9 and MMP-3 in glomerulus of IMN group increased as compared to those in the control group (P < 0.05). TIMP-1 was expressed at a low level in tubular epithelial cells and no expression of TIMP-1 could be detected in glomerulus of control group. TIMP-1 was expressed in podocytes and tubular epithelial cells of IMN group. In the IMN group, the expression of TIMP-1 and 24h urine protein quantitation were obviously increased as compared to those in the control group (P < 0.01). In comparison with I stage MN group, the average MMP-9 /TIMP-1 ratio of II stage MN group was significantly decreased (P < 0.01), as well as the average MMP-3 /TIMP-1 ratio (P < 0.01). In IMN group, the expression of MMP-9 was negatively correlated with the level of serum creatinine (r= 0.02,P < 0.05), and the expression of TIMP-1 was positively correlated with serum crealinine (r=0.34, P<0.05). Conclusions MMP-9 and TIMP-1 affect renal function in negative and positive manners respectively. In IMN, the abnormal expression of MMPs may be correlated with albuminuria, and the disbalance of MMP/TIMP ratio may be correlated with glomerular incrassate basement membrane.