2型糖尿病不同尿白蛋白阶段患者血清sKlotho和NGAL水平变化及其相关性
The changes of serum sKlotho and NGAL levels and their correlation in type 2 diabetes mellitus patients with different stages of urinary albumin.
作者信息
Wu Can, Wang Qiuyue, Lv Chuan, Qin Ningning, Lei Sha, Yuan Qin, Wang Guan
机构信息
Department of Endocrinology, The First Hospital Affiliated to China Medical University, Shenyang 110001, China.
Department of Endocrinology, The First Hospital Affiliated to China Medical University, Shenyang 110001, China.
出版信息
Diabetes Res Clin Pract. 2014 Nov;106(2):343-50. doi: 10.1016/j.diabres.2014.08.026. Epub 2014 Sep 16.
OBJECTIVE
To investigate the changes of serum anti-aging protein Klotho and neutrophil gelatinase-associated lipocalin (NGAL) levels and their correlation in type 2 diabetes mellitus (T2DM) patients at different stages of diabetic kidney disease (DKD) determined by urinary albuminuria.
METHODS
462 cases with T2DM were divided into three groups: normoalbuminuric [N-UAlb; urinary albumin to creatinine ratio (UACR) < 30 mg/g, n=180], microalbuminuric [M-UAlb; UACR 30-300 mg/g, n = 158], macroalbuminuric [L-UAlb; UACR > 300 mg/g, n = 124]. The levels of serum soluble-Klotho (sKlotho), NGAL, 8-isoprostane prostaglandin F2α (8-iso-PGF2α), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) were determined by enzyme-linked immunosorbent assay (ELISA) in all cases and 160 control subjects.
RESULTS
Compared with control, serum sKlotho levels were significantly decreased (P < 0.001), and serum NGAL levels increased significantly (P < 0.001) in T2DM patients. Furthermore, serum sKlotho and NGAL levels were significantly negatively correlated (P < 0.001). Serum sKlotho levels negatively correlated with UACR, TG, CHO, LDL, 8-Iso-PGF2α, MCP-1, TNF-α, TGF-β1 (P < 0.001), but positively correlated with LDL (P < 0.001). Serum NGAL levels positively correlated with UACR, 8-Iso-PGF2α, MCP-1, TNF-α, TGF-β1 (P < 0.001). In addition, serum NGAL levels and LDL were significantly positively correlated (P = 0.005), and HDL was significantly negatively correlated (P < 0.001).
CONCLUSION
Serum Klotho and NGAL levels may become new biomarkers of the early diagnosis of DKD in T2DM. Klotho may participate in the development of DKD pathological mechanism such as oxidative stress related to inflammation, renal fibrosis, lipid metabolic disorders, modulating the pathological process of diabetic kidney tissue. NGAL may play a part in these mechanisms.
目的
通过尿白蛋白尿来研究2型糖尿病（T2DM）患者在糖尿病肾病（DKD）不同阶段血清抗衰老蛋白α-klotho（Klotho）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）水平的变化及其相关性。
方法
将462例T2DM患者分为三组：正常白蛋白尿组[N-UAlb；尿白蛋白与肌酐比值（UACR）<30 mg/g，n = 180]、微量白蛋白尿组[M-UAlb；UACR 30 - 300 mg/g，n = 158]、大量白蛋白尿组[L-UAlb；UACR>300 mg/g，n = 124]。采用酶联免疫吸附测定（ELISA）法测定所有病例及160例对照者血清可溶性Klotho（sKlotho）、NGAL、8-异前列腺素F2α（8-iso-PGF2α）、单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子-α（TNF-α）、转化生长因子-β1（TGF-β1）水平。
结果
与对照组相比，T2DM患者血清sKlotho水平显著降低（P<0.001），血清NGAL水平显著升高（P<0.001）。此外，血清sKlotho与NGAL水平呈显著负相关（P<0.001）。血清sKlotho水平与UACR、甘油三酯（TG）、总胆固醇（CHO）、低密度脂蛋白（LDL）、8-异前列腺素F2α、MCP-1、TNF-α、TGF-β1呈负相关（P<0.001），但与高密度脂蛋白（HDL）呈正相关（P<0.001）。血清NGAL水平与UACR、8-异前列腺素F2α、MCP-1、TNF-α、TGF-β1呈正相关（P<0.001）。此外，血清NGAL水平与LDL呈显著正相关（P = 0.005），与HDL呈显著负相关（P<0.001）。
结论
血清Klotho和NGAL水平可能成为T2DM患者DKD早期诊断的新生物标志物。Klotho可能参与DKD病理机制的发展，如与炎症、肾纤维化、脂质代谢紊乱相关的氧化应激，调节糖尿病肾组织的病理过程。NGAL可能在这些机制中发挥作用。
Zotero 插件