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血液透析患者的血清金属蛋白酶 MMP-2、MMP-9 以及金属蛋白酶组织抑制剂 TIMP-1 和 TIMP-2。

Serum metalloproteinases MMP-2, MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in patients on hemodialysis.

机构信息

Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Lodz, Poland.

出版信息

Int Urol Nephrol. 2011 Jun;43(2):491-8. doi: 10.1007/s11255-009-9683-1. Epub 2009 Dec 2.

DOI:10.1007/s11255-009-9683-1
PMID:19953348
Abstract

BACKGROUND

We assessed the effect of hemodialysis (HD) and chronic kidney disease (CKD) on the serum levels of metalloproteinase-2 (MMP-2), MMP-9 and metalloproteinase tissue inhibitors (TIMP-1) and TIMP-2.

METHODS

18 patients on regular HD treatment with low-flux, cuprophane membrane, 15 non-dialyzed patients with CKD and 15 healthy controls were sampled. The serum MMP and TIMP concentrations were determined by ELISA assays.

RESULTS

MMP-9, TIMP-1, and TIMP-2 serum levels were significantly decreased in HD patients to 32.7 ± 20.1 ng/ml, 178.8 ± 73.0 ng/ml, and 103.4 ± 55.3 ng/ml compared with 482.3 ± 139.5, 367.6 ± 75.5 ng/ml, and 299.7 ± 63.2 ng/ml in patients with CKD and 594.6 ± 154.7 ng/ml, 354.5 ± 81.2 ng/ml, and 272.4 ± 91.8 ng/ml in healthy controls, respectively, (P < 0.001 vs. HD patients). MMP-2 was lower in patients with CKD: 405.6 ± 106.1 ng/ml compared with 516.9 ± 81.7 ng/ml in controls (P = 0.02). The MMP-2/TIMP-2 ratio was increased in HD patients compared with both patients with CKD and controls. In the course of an HD session, MMP-2 and TIMP-1 serum levels were significantly decreased from pre-HD 570.0 ± 256.5 and 178.8 ± 66.9 ng/ml to post-HD 492.6 ± 212.5 and 144.6 ± 44.2 ng/ml (P = 0.004 and 0.013, respectively). However, the MMP-9/TIMP-1 ratio increased from pre-HD 0.15 (2.19) (median, range) to 0.23 (0.33) after a HD session (P = 0.03). CRP was positively correlated with MMP-9 and MMP-9/TIMP-1 ratio in HD patients and patients with CKD (r = 0.67; P = 0.03).

CONCLUSIONS

The MMP-9/TIMP-1 ratio increased during HD sessions, although their absolute levels were lowered. This change may represent a chronic state of enhanced fibrosis in patients undergoing HD.

摘要

背景

我们评估了血液透析(HD)和慢性肾脏病(CKD)对血清基质金属蛋白酶-2(MMP-2)、MMP-9 和基质金属蛋白酶组织抑制剂(TIMP-1)和 TIMP-2 水平的影响。

方法

18 例接受高通量、铜仿膜常规 HD 治疗的患者、15 例未透析的 CKD 患者和 15 例健康对照者被纳入研究。通过 ELISA 检测血清 MMP 和 TIMP 浓度。

结果

与 CKD 患者的 482.3 ± 139.5ng/ml、367.6 ± 75.5ng/ml 和 299.7 ± 63.2ng/ml 以及健康对照组的 594.6 ± 154.7ng/ml、354.5 ± 81.2ng/ml 和 272.4 ± 91.8ng/ml 相比,HD 患者的 MMP-9、TIMP-1 和 TIMP-2 血清水平分别显著下降至 32.7 ± 20.1ng/ml、178.8 ± 73.0ng/ml 和 103.4 ± 55.3ng/ml(P < 0.001)。CKD 患者的 MMP-2 水平较低,为 405.6 ± 106.1ng/ml,与对照组的 516.9 ± 81.7ng/ml 相比,差异有统计学意义(P = 0.02)。与 CKD 患者和对照组相比,HD 患者的 MMP-2/TIMP-2 比值增加。在 HD 治疗过程中,MMP-2 和 TIMP-1 血清水平从治疗前的 570.0 ± 256.5ng/ml 和 178.8 ± 66.9ng/ml 显著下降至治疗后的 492.6 ± 212.5ng/ml 和 144.6 ± 44.2ng/ml(P = 0.004 和 0.013)。然而,MMP-9/TIMP-1 比值从治疗前的 0.15(2.19)(中位数,范围)增加到治疗后的 0.23(0.33)(P = 0.03)。CRP 与 HD 患者和 CKD 患者的 MMP-9 和 MMP-9/TIMP-1 比值呈正相关(r = 0.67;P = 0.03)。

结论

尽管 MMP-9/TIMP-1 比值在 HD 期间升高,但绝对水平下降。这种变化可能代表接受 HD 治疗的患者存在慢性纤维化增强状态。

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