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

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

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(?)(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24 h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。

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 （IMN）, 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 ceils, interstifium and podocytes of control group. MMP-9 and MMP-3 were expressed in podocytes, mesangial cells, glomerular basement membrane and tubular epithelial ceils 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 ceils 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 〈 0.0l）, 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 creatinine （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.