金属蛋白酶组织抑制因子-1在糖尿病肾病患者中的表达

Study on serum levels of TIMP-1 in patients with diabetic nephropathy

目的观察金属蛋白酶组织抑制因子-1(TIMP-1)在糖尿病肾病不同临床阶段的变化规律,进而探讨TIMP-1在糖尿病肾病发生、发展过程中的作用。方法选取健康对照组(NC)20例,2型糖尿病组(DM)20例,临床期糖尿病肾病组(DN)20例及糖尿病肾病肾功能衰竭组(DNF)20例为研究对象,利用酶联免疫吸附实验(ELISA)分别检测各试验对象血清中TIMP-1的含量,采用方差分析和q检验比较各组TIMP-1水平的差异性;TIMP-1在不同性别间的差异分析用t检验,TIMP-1水平与年龄的关系采用直线相关分析和t检验。结果正常对照组血清TIMP-1水平为825.97±137.34(ng/ml),糖尿病组1259.05±218.47(ng/ml),临床期糖尿病肾病组1508.31±282.57(ng/ml),糖尿病肾病肾功能衰竭组2131.42±441.25(ng/ml)。糖尿病组、临床期糖尿病肾病组及糖尿病肾功能衰竭组血清中TIMP-1水平比正常对照组显著增高(P均<0.01)。临床期糖尿病肾病组比糖尿病组、糖尿病肾病肾功能衰竭组比临床期糖尿病肾病组的TIMP-1水平也明显增高(P<0.05,P<0.01)。TIMP-1血清水平在性别间的差异无统计学意义。在DM组和DNF组,TIMP-1水平与年龄正相关,相关系数r分别为0.4866(P<0.05)和0.6229(P<0.01),两相关系数差异无显著性。结论随着糖尿病肾病的病情进展,血清中TIMP-1水平逐渐增高,提示TIMP-1可能参与了糖尿病患者动脉硬化、动脉粥样斑块的形成及高血压的血管重塑过程;TIMP-1可能介导了肾小球细胞外基质(ECM)积聚、肾小球基底膜(GBM)重塑、肾小球硬化,在糖尿病肾病发生、发展过程中起着重要作用。

Objective To investigate the serum levels of tissue-inhihitor of metaUoproteinase-1 （TIMP-1） in different clinical stages of patients with diabetic nephropathy, to explore the role of TIMP-1 in the development and progression of diabetic nephropathy. Methods Eighty people were sampled, including normal control group （NC, n= 20 ）, type 2 diabetic mellitus（DM, n = 20 ）, clinical stage of diabetic nephropathy（DN, n = 20） and renal failure stage of diabetic nephropathy（ DNF, un= 20）. Serum concentrations of TIMP-1 from all subjects were detected by enzyme-linked immunosorbentassay（ELISA） then analyse statistically the difference of TIMP-1 level between groups and between sex with analysis of variance,q-test （Student-Newman-Keuls） and t-test.The relativity of TIMP-1 level and age were checked with correlation analysis and t-test.Results Serum levels of TIMP-1 were 825.97 ± 137.34 ng/ ml, 1259.05 ± 218.47 ng/ml, 1508.31 ± 282.57 ng/ml and 2131.42± 441.25 ng/ml in NC, DM, DN and DNF respectively. Levels of TIMP-1 in patients with DM, DN and DNF were more significantly elevated than those in normal control group（ P 〈 0.01 ）. Patients with DN had higher TIMP-1 compared with DM patients （P〈 0.05）.In addition,patients with DNF had significantly higher TIMP-1 compared with DN patients（ P 〈 0.01 ）. There was no statistical significance between sex（ P 〉 0.05）, but the concentrations of TIMP- 1 were associated with ages in DM and DNF Groups, the coefficient of correlation was 0.4866（ P 〈 0.05） and 0.6229 （ P 〈 0.01 ）. Them was no apparent statistical difference between the cocfficient of correlations. Conclusion Serum levels of TIMP-1 were gradually increasing with the progression of diabetic nephropathy.The results strongly suggested that TIMP-1 may contribute to vascular remodeling during the development and progression of high blood pressure and atherosclerosis. Meanwhile,TIMP-1 may mediate remodeling of glomerular basement membrane（GBM） and glomemlosclerosis and plays an important role in the development and progression of diabetic nephropathy.