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早期糖尿病肾病患者血清基质金属蛋白酶-9、金属蛋白酶组织抑制剂-1及基质金属蛋白酶-9/中性粒细胞明胶酶相关脂质运载蛋白复合物水平

Serum Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1 and Matrix Metalloproteinase-9/ Neutrophil Gelatinase-associated Lipocalin Complex Levels in Patients With Early-stage Diabetic Nephropathy.

作者信息

Cakirca Gokhan, Turgut Faruk Hilmi

机构信息

Department of Biochemistry, Sanliurfa Mehmet Akif Inan Training and Research Hospital, Sanliurfa, Turkey.

出版信息

Iran J Kidney Dis. 2018 Oct;12(5):299-304.

Abstract

INTRODUCTION

This study was aimed to investigate the efficacy of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and the neutrophil gelatinase-associated lipocalin (NGAL)-bound form of MMP-9 (MMP-9/NGAL complex) markers in the determination of early nephropathy in patients with type 2 diabetes mellitus.

MATERIALS AND METHODS

Twenty-five type 2 diabetic patients with normoalbuminuria, 27 type 2 diabetic patients with microalbuminuria, and 23 healthy controls were recruited. Serum levels of MMP-9, TIMP-1, and MMP9/NGAL complex were measured in all participants.

RESULTS

The MMP-9 level and MMP-9/TIMP-1 ratio were higher in patients with microalbuminuria when compared to the controls, while TIMP-1 level was lower (P = .005, P = .006, and P = .02, respectively). The MMP-9 level and MMP-9/TIMP-1 ratio were significantly higher in the patients with normoalbuminuria when compared to the controls (P = .005 and P = .02, respectively). In the normoalbuminuric patients, MMP-9 levels were negatively correlated with estimated GFR (r = -0.553, P = .008) and positively correlated with glucose (r = 0.449, P = .04), creatinine (r = 0.454, P = .03), and MMP9/NGAL complex (r = 0.575, P = .005). In the microalbuminuric patients, MMP-9 levels were positively correlated with total cholesterol (r = 0.430, P = .03), and MMP9/NGAL complex (r = 0.650, P = .001).

CONCLUSIONS

The levels of MMP-9, TIMP-1, and MMP9/NGAL complex were similar in microalbuminuric and normoalbuminuric patients with type 2 diabetes mellitus. However, there was a significant MMP-9/TIMP-1 imbalance in both groups which may reflect impaired extracellular matrix homeostasis.

摘要

引言

本研究旨在探讨基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制剂-1(TIMP-1)以及中性粒细胞明胶酶相关脂质运载蛋白结合形式的MMP-9(MMP-9/NGAL复合物)标志物在2型糖尿病患者早期肾病判定中的作用。

材料与方法

招募了25例正常白蛋白尿的2型糖尿病患者、27例微量白蛋白尿的2型糖尿病患者以及23名健康对照者。检测了所有参与者血清中MMP-9、TIMP-1和MMP9/NGAL复合物的水平。

结果

与对照组相比,微量白蛋白尿患者的MMP-9水平及MMP-9/TIMP-1比值更高,而TIMP-1水平更低(P值分别为0.005、0.006和0.02)。与对照组相比,正常白蛋白尿患者的MMP-9水平及MMP-9/TIMP-1比值也显著更高(P值分别为0.005和0.02)。在正常白蛋白尿患者中,MMP-9水平与估算的肾小球滤过率呈负相关(r = -0.553,P = 0.008),与血糖(r = 0.449,P = 0.04)、肌酐(r = 0.454,P = 0.03)及MMP9/NGAL复合物(r = 0.575,P = 0.005)呈正相关。在微量白蛋白尿患者中,MMP-9水平与总胆固醇(r = 0.430,P = 0.03)及MMP9/NGAL复合物(r = 0.650,P = 0.001)呈正相关。

结论

2型糖尿病微量白蛋白尿和正常白蛋白尿患者的MMP-9、TIMP-1及MMP9/NGAL复合物水平相似。然而,两组均存在显著的MMP-9/TIMP-1失衡,这可能反映了细胞外基质稳态受损。

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