糖尿病肾病中的血清基质金属蛋白酶MMP - 2和MMP - 9以及金属蛋白酶组织抑制剂TIMP - 1和TIMP - 2

Serum matrix metalloproteinases MMP-2 and MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in diabetic nephropathy.

作者信息

Rysz Jacek, Banach Maciej, Stolarek Robert A, Pasnik Jaroslaw, Cialkowska-Rysz Aleksandra, Koktysz Robert, Piechota Mariusz, Baj Zbigniew

机构信息

Second Department of Family Medicine, Medical University of Lodz, Lodz, Poland.

出版信息

J Nephrol. 2007 Jul-Aug;20(4):444-52.

PMID:17879211

Abstract

BACKGROUND

The regulation of mesangial extracellular matrix (ECM) turnover engages a number of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). High glucose concentration affects ECM degradation and the activities of MMPs and TIMPs. ECM accumulation is involved in the pathogenesis of diabetic nephropathy.

METHODS

Serum MMP-9, MMP-2, TIMP-2 and TIMP-1 were measured with ELISA in patients with either chronic renal failure (CRF, n=20), type 2 diabetes mellitus (DM2, n=16) or diabetic nephropathy (DM2+CRF, n=14), and healthy controls (n=20).

RESULTS

Diabetic nephropathy was related with profound decrease of serum TIMP-2 (122.2 +/- 47.2 vs. 263.0 +/- 89.2 ng/mL), TIMP-1 (242.5 +/- 96.9 vs. 347.4 +/- 87.2 ng/mL) and MMP-2 (385.4 +/- 42.6 vs. 517.2 +/- 75.4 ng/mL) (p<0.001). Both TIMP-1 and TIMP-2 were reduced in diabetic nephropathy in comparison with either diabetes alone (p<0.01 and p<0.001; respectively) or CRF alone (p<0.001 for both). An approximately 2-fold increase of MMP-9/TIMP-1 and MMP-2/TIMP-2 ratio was found in diabetic nephropathy when compared with diabetes with normal renal function (p<0.01). Further, in DM2 patients, TIMP-2 was decreased when compared with CRF alone (219.2 +/- 71.8 vs. 296.8 +/- 58.4 ng/mL). MMP-2 was lowered in both groups of DM2 and CRF patients (413.8 +/- 59.0 ng/mL and 409.7 +/- 93.1 ng/mL, vs. normal control value of 517.2 +/- 75.4 ng/mL; p<0.001).

CONCLUSIONS

These data indicate that circulating TIMP-1, TIMP-2 and MMP-2 are decreased in patients with diabetic nephropathy when compared with either CRF or diabetes.

摘要

背景

肾小球系膜细胞外基质（ECM）周转的调节涉及多种基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）。高血糖浓度会影响ECM降解以及MMPs和TIMPs的活性。ECM积累参与糖尿病肾病的发病机制。

方法

采用酶联免疫吸附测定法（ELISA）检测慢性肾衰竭患者（CRF，n = 20）、2型糖尿病患者（DM2，n = 16）、糖尿病肾病患者（DM2 + CRF，n = 14）以及健康对照者（n = 20）血清中的MMP - 9、MMP - 2、TIMP - 2和TIMP - 1水平。

结果

糖尿病肾病患者血清TIMP - 2（122.2±47.2对263.0±89.2 ng/mL）、TIMP - 1（242.5±96.9对347.4±87.2 ng/mL）和MMP - 2（385.4±42.6对517.2±75.4 ng/mL）显著降低（p<0.001）。与单纯糖尿病（分别为p<0.01和p<0.001）或单纯CRF相比，糖尿病肾病患者的TIMP - 1和TIMP - 2均降低（两者均为p<0.001）。与肾功能正常的糖尿病患者相比，糖尿病肾病患者的MMP - 9/TIMP - 1和MMP - 2/TIMP - 2比值增加了约2倍（p<0.01）。此外，在DM2患者中，与单纯CRF相比，TIMP - 2降低（219.2±71.8对296.8±58.4 ng/mL）。DM2和CRF患者组的MMP - 2均降低（分别为413.8±59.0 ng/mL和409.7±93.1 ng/mL，而正常对照值为517.2±75.4 ng/mL；p<0.001）。