2型糖尿病患者血清抗衰老蛋白Klotho的临床意义  

Clinical significance and different levels of serum Klotho in type 2 diabetic patients

作　　者：吴灿[1] 王秋月[1] 吕川[1] 秦宁宁[1] 雷莎[1] 袁琴[1] 王冠[2] 

机构地区：[1]中国医科大学附属第一医院内分泌科,沈阳110001 [2]中国医科大学临床医学系

出　　处：《中华糖尿病杂志》2015年第3期177-181,共5页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：辽宁省科技攻关计划项目（2011225017）;辽宁省“百千万人才工程”资助项目（2011年）

摘　　要：研究旨在探讨2型糖尿病（T2DM）患者血清抗衰老蛋白Klotho在糖尿病肾病（DN）不同阶段的水平差异及其临床意义。纳入2010年4月至2013年7月T2DM患者462例，男214例，女248例，年龄（53＆#177;6）岁。根据尿白蛋白/肌酐比率（UACR）分为糖尿病正常白蛋白尿（N）组（〈30 mg/g，180例）、微量白蛋白尿（M）组（30-300 mg/g，158例）和大量白蛋白尿（L）组（〉300 mg/g，124例）。选取同期体检中心年龄相匹配的健康志愿者160名为正常对照（NC）组，男78名，女82名，年龄（51＆#177;6）岁。采用酶联免疫吸附法（ELISA）检测血清游离Klotho（sKlotho）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、8-异前列腺素F2α（8-iso-PGF2α）以及其他炎症因子水平。多元回归分析各血清指标与尿白蛋白间的关系。结果发现：（1）与NC组[377.2（359.5-394.9）ng/L]相比，N组[246.1（236.1-256.2）ng/L]血清sKlotho水平明显下降（P〈0.05），大量蛋白尿组血清sKlotho水平最低[90.1（83.1-97.0）ng/L]。（2）血清sKlotho水平与NGAL、UACR水平呈显著负相关（r=-0.491、-0.732，均P〈0.05），与预估肾小球滤过率（eGFR）呈显著正相关（r=0.344，P〈0.05），与血清8-Iso-PGF2α、单核细胞趋化蛋白1、肿瘤坏死因子α、转化生长因子β1水平呈显著负相关（r=-0.437、-0.358、-0.422、-0.461，均P〈0.05）。研究表明血清sKlotho水平可能成为早期诊断DN的新型生物标志蛋白，其机制可能涉及氧化应激、肾脏纤维化等。This study is to investigate the changes of serum anti-aging protein Klotho levels and its correlation with other serum indexes in type 2 diabetes mellitus（T2DM）patients at different stages of diabetic kidney disease（DN）. A total of 462 cases with T2DM were divided into three groups according to the level of urinary albumin to creatinine ratio（UACR）：normoal buminuric group（group N,UACR〈30 mg/g,n=180）,microalbuminuric group（group M,UACR 30-300 mg/g,n=158）,and macro-albuminuric group （group L,UACR〉300 mg/g,n=124）,while 160 healthy volunteers age-matched were selected as the normal control（NC）group,78 males and 82 females,age（51 ＆#177; 6）yrs. The levels of serum soluble-Klotho（sKlotho）, neutrophil gelatinase- associated lipocalin （NGAL）,8- isoprostane prostaglandin F2α（8-iso-PGF2α）, monocyte chemotactic protein-1（MCP-1）,tumor necrosis factor-α（TNF-α）and transforming growth factor-β1（TGF-β1）were determined by a quantitative sandwich enzyme-linked immuno sorbent assay（ELISA）in all the cases and 160 subjects of control（group NC）. Multiple regression analysis was used to analyze the relationship between the various indexes of serum and urinary albumin. The results showed as following：（1） Compared with group NC,the levels of serum sKlotho in group N was obviously decreased（377.2（359.5-394.9） ng/L vs 246.1（236.1-256.2）ng/L,P〈0.05）,especially in group L（90.1（83.1-97.0）ng/L）.（2）The serum sKlotho levels were significantly negative in correlation with NGAL and UACR levels（r=-0.491,-0.732,both P〈0.05）,but positively correlated with estimated glomerular filtration rate（eGFR,r=0.344,P〈0.05）. The levels of serum sKlotho was negatively correlated to the levels of serum 8-Iso-PGF2α,MCP-1, TNF-α,TGF-β1（r=-0.437,-0.358,-0.422,-0.461,all P〈0.05）. The results suggest that the serum levels of Klotho may become new biological maker proteins of early diagnosing DN in T2DM. The mechanisms may be involved in oxi

关 键 词：糖尿病肾病 白蛋白尿 抗衰老酶 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]