糖尿病患者血清sKlotho、NGAL、MCP-1和TGF-β1的表达及意义
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摘要
目的探讨2型糖尿病患者血清分泌型Klotho(sKlotho)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、单核趋化蛋白1(MCP-1)、转化生长因子β1(TGF-β1)表达水平及意义。方法将252例2型糖尿病患者根据尿白蛋白/肌酐比率(UACR)分为正常尿白蛋白组(UACR <30 mg/g)、微量尿白蛋白组(30 mg/g≤UACR <300 mg/g)和大量尿白蛋白组(UACR≥300 mg/g);另选同期100例身体健康者为健康对照组。收集受试者尿白蛋白、血尿肌酐,估算肾小球滤过率(eGFR)、糖化血红蛋白(HbA1c)、空腹血糖(FPG)、口服糖耐量试验2 h血糖(2 h PG)、胰岛素抵抗指数(HOMA-IR)、总胆固醇(TC)以及三酰甘油(TG)指标;酶联免疫(ELISA)检测血清sKlotho、NGAL、MCP-1、TGF-β1水平。结果 2型糖尿病患者的收缩压较健康对照组显著升高(P <0. 05);正常尿白蛋白组和大量尿白蛋白组的舒张压较健康对照组显著升高(P <0. 05)。2型糖尿病患者的eGFR、HbA1c、FPG、2 h PG、TC、TG水平随病情的加重逐渐增加(P <0. 05)。ELISA结果显示,2型糖尿病患者sKlotho水平随病情的加重逐渐降低(P <0. 05),NGAL、MCP-1、TGF-β1水平随病情加重逐渐增加(P <0. 05)。2型糖尿病患者血清sKlotho水平与UACR、HbA1c、FPG、2 h PG、HOMA-IR、TC、TG呈负相关(P <0. 05),与e GFR呈正相关(P <0. 05);血清NGAL、MCP-1、TGF-β1水平与体重指数、UACR、HbA1c、FPG、2 h PG、HOMA-IR、TC、TG呈正相关(P <0. 05),与eGFR呈负相关(P <0. 05)。结论血清s Klotho、NGAL、MCP-1、TGF-β1水平可能成为2型糖尿病的早期诊断标志物,其机制可能与炎性反应、肾脏损伤等有关。
Objective To explore the expression and significance of serum secreting type s Klotho( s Klotho),neutrophil gelatinase-associated lipocalin( NGAL),monocyte chemoattractant protein 1( MCP-1) and transforming growth factor β1( TGF-β1) in patients with type 2 diabetes mellitus( T2DM). Methods A total of 252 patients with T2DM were divided into normal urine albumin group( UACR < 30mg/g),microalbuminuria group( 30mg/g < UACR < 300mg/g) and large urinary albumin groups( UACR > 300mg/g) according to the urinary albumin/creatinine ratio( UACR),at the same time,the other 100 healthy subjects were enrolled as control group. The levels of urinary albumin,hematuria creatinine,estimated glomerular filtration rate( eGFR),glycosylated hemoglobin( HbA1c),fasting blood glucose( FPG),oral glucose tolerance test blood glucose 2h( 2h PG) and insulin resistance index( HOMA-IR),total cholesterol( TC) and trigalloyl glycerol( TG) were detected and compared among groups. In addition,enzyme linked immunosorbent assay( ELISA) was used to detect the serum levels of s Klotho,NGAL,MCP-1 and TGF-β1. Results The systolic blood pressure in patients with T2DM was significantly higher than that in control group( P < 0. 05). The levels of diastolic blood pressure of patients in normal urine albumin group and large urine albumin group were significantly higher than those in control group( P < 0. 05).Moreover,the levels of eGFR,HbA1c,FPG,2 h PG,TC,TG,NGAL,MCP1 and TGF-β1 of patients with T2DM were increased gradually,and the levels of s Klotho were decreased gradually with the aggravation of disease( P < 0. 05). In addition,the serum levels of s Klotho were negatively correlated with those of UACR,HbA1c,FPG,2h PG,HOMAIR,TC and TG( P < 0. 05),however,which were positively correlated with those of eGFR( P < 0. 05). The serum levels of NGAL,MCP1 and TGF-β1 were positively correlated with body mass index,UACR,HbA1c,FPG,2h PG,HOMAIR,TC and TG( P <0. 05),however,which were negatively correlated with eGFR( P < 0. 05). Conclusion The serum levels of s Klotho,NGAL,MCP1 and TGF-β1 may be regarded as the markers of early diagnosis of T2DM,and its mechanism may be related to inflammatory reaction and kidney injury.
Objective To explore the expression and significance of serum secreting type s Klotho( s Klotho),neutrophil gelatinase-associated lipocalin( NGAL),monocyte chemoattractant protein 1( MCP-1) and transforming growth factor β1( TGF-β1) in patients with type 2 diabetes mellitus( T2DM). Methods A total of 252 patients with T2DM were divided into normal urine albumin group( UACR < 30mg/g),microalbuminuria group( 30mg/g < UACR < 300mg/g) and large urinary albumin groups( UACR > 300mg/g) according to the urinary albumin/creatinine ratio( UACR),at the same time,the other 100 healthy subjects were enrolled as control group. The levels of urinary albumin,hematuria creatinine,estimated glomerular filtration rate( eGFR),glycosylated hemoglobin( HbA1c),fasting blood glucose( FPG),oral glucose tolerance test blood glucose 2h( 2h PG) and insulin resistance index( HOMA-IR),total cholesterol( TC) and trigalloyl glycerol( TG) were detected and compared among groups. In addition,enzyme linked immunosorbent assay( ELISA) was used to detect the serum levels of s Klotho,NGAL,MCP-1 and TGF-β1. Results The systolic blood pressure in patients with T2DM was significantly higher than that in control group( P < 0. 05). The levels of diastolic blood pressure of patients in normal urine albumin group and large urine albumin group were significantly higher than those in control group( P < 0. 05).Moreover,the levels of eGFR,HbA1c,FPG,2 h PG,TC,TG,NGAL,MCP1 and TGF-β1 of patients with T2DM were increased gradually,and the levels of s Klotho were decreased gradually with the aggravation of disease( P < 0. 05). In addition,the serum levels of s Klotho were negatively correlated with those of UACR,HbA1c,FPG,2h PG,HOMAIR,TC and TG( P < 0. 05),however,which were positively correlated with those of eGFR( P < 0. 05). The serum levels of NGAL,MCP1 and TGF-β1 were positively correlated with body mass index,UACR,HbA1c,FPG,2h PG,HOMAIR,TC and TG( P <0. 05),however,which were negatively correlated with eGFR( P < 0. 05). Conclusion The serum levels of s Klotho,NGAL,MCP1 and TGF-β1 may be regarded as the markers of early diagnosis of T2DM,and its mechanism may be related to inflammatory reaction and kidney injury.
引文
1汪会琴,胡如英,武海滨,等.2型糖尿病报告发病率研究进展.浙江预防医学,2016,28:37-39.
2呙劲松,陈艳.甘精胰岛素对新诊断2型糖尿病患者血清炎症反应的影响.中国临床研究,2015,28:40-42.
3吴灿,王秋月,吕川,等.2型糖尿病患者血清抗衰老蛋白Klotho的临床意义.中国糖尿病杂志,2015,7:177-181.
4吴灿,吕川,周月宏,等.抗衰老蛋白Klotho阻断高糖培养的大鼠肾小球系膜细胞TLR4/NF-kB p65/NGAL通路的激活及其作用机制.中华内分泌代谢杂志,2015,31:611-617.
5戴晓康,邢燕,叶山东.二甲双胍对2型糖尿病患者尿单核细胞趋化蛋白-1排泄的影响.中国糖尿病杂志,2016,24:123-126.
6李晓丽,刘玲玲,赵龙,等.2型糖尿病患者血浆TGF-β1水平及其与心脏结构和功能的关系.江苏大学学报(医学版),2015,25:317-321.
7中华医学会糖尿病学分会.中国2型糖尿病防治指南.中华糖尿病杂志,2014,6:447-498.
8侯清涛,李芸,李舍予,等.全球糖尿病疾病负担现状.中国糖尿病杂志,2016,24:92-96.
9董琪,李全民.糖尿病周围神经病变发病机制的研究进展.现代仪器与医疗,2015,22:20-22.
10李伟,张晨鑫,王玲,等.2型糖尿病合并肥胖患者腹部脂肪分布与胰岛素抵抗的相关性研究.重庆医学,2017,46:3632-3634.
11杨立勇.关注糖尿病微血管并发症研究进展.中国糖尿病杂志,2016,8:449-451.
12叶爱丽,赵红霞,龚利亚.2型糖尿病患者发生慢性并发症的时间与相关因素研究.中国现代医学杂志,2016,26:139-142.
13 Oh HJ,Nam BY,Lee MJ,et al.Decreased circulating klotho levels in patients undergoing dialysis and relationship to oxidative stress and inflammation.Peritoneal Dialysis International Journal of the International Society for Peritoneal Dialysis,2015,35:43-51.
14 Buendía P,Carracedo J,Soriano S,et al.Klotho Prevents NF Btranslocation and protects endothelial cell from senescence induced by uremia.Journals of Gerontology,2015,70:1198-1209.
15 De Sliva PM,Mohammed Abdul KS,Eakanayake EM,et al.Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology(CKDu)among Agricultural Communities in Sri Lanka.Plos Neglected Tropical Diseases,2016,10:e0004979.
16郭露露,赵卫红.NGAL与肾脏疾病研究进展.中华肾脏病杂志,2015,31:156-160.
17 Vohr HW.Monocyte Chemoattractant Protein 1(MCP-1).Cytokine,2016,60:1-12.
18 Jeon HJ,Choi HJ,Park BH,et al.Association of monocyte chemoattractant protein-1(MCP-1)2518A/G polymorphism with proliferative diabetic retinopathy in Korean type 2 diabetes.Yonsei Medical Journal,2013,54:621-625.
19高巍,武忠,李敏州,等.中医药基于TGF-β1治疗糖尿病肾病研究概况.中医药临床杂志,2017,29:164-167.
20 Jazi MF,Biglari A,Mazloomzadeh S,et al.Recombinant fibromodulin has therapeutic effects on diabetic nephropathy by down-regulating transforming growth factor-β1 in streptozotocin-induced diabetic rat model.Iranian Journal of Basic Medical Sciences,2016,19:265-271.
2呙劲松,陈艳.甘精胰岛素对新诊断2型糖尿病患者血清炎症反应的影响.中国临床研究,2015,28:40-42.
3吴灿,王秋月,吕川,等.2型糖尿病患者血清抗衰老蛋白Klotho的临床意义.中国糖尿病杂志,2015,7:177-181.
4吴灿,吕川,周月宏,等.抗衰老蛋白Klotho阻断高糖培养的大鼠肾小球系膜细胞TLR4/NF-kB p65/NGAL通路的激活及其作用机制.中华内分泌代谢杂志,2015,31:611-617.
5戴晓康,邢燕,叶山东.二甲双胍对2型糖尿病患者尿单核细胞趋化蛋白-1排泄的影响.中国糖尿病杂志,2016,24:123-126.
6李晓丽,刘玲玲,赵龙,等.2型糖尿病患者血浆TGF-β1水平及其与心脏结构和功能的关系.江苏大学学报(医学版),2015,25:317-321.
7中华医学会糖尿病学分会.中国2型糖尿病防治指南.中华糖尿病杂志,2014,6:447-498.
8侯清涛,李芸,李舍予,等.全球糖尿病疾病负担现状.中国糖尿病杂志,2016,24:92-96.
9董琪,李全民.糖尿病周围神经病变发病机制的研究进展.现代仪器与医疗,2015,22:20-22.
10李伟,张晨鑫,王玲,等.2型糖尿病合并肥胖患者腹部脂肪分布与胰岛素抵抗的相关性研究.重庆医学,2017,46:3632-3634.
11杨立勇.关注糖尿病微血管并发症研究进展.中国糖尿病杂志,2016,8:449-451.
12叶爱丽,赵红霞,龚利亚.2型糖尿病患者发生慢性并发症的时间与相关因素研究.中国现代医学杂志,2016,26:139-142.
13 Oh HJ,Nam BY,Lee MJ,et al.Decreased circulating klotho levels in patients undergoing dialysis and relationship to oxidative stress and inflammation.Peritoneal Dialysis International Journal of the International Society for Peritoneal Dialysis,2015,35:43-51.
14 Buendía P,Carracedo J,Soriano S,et al.Klotho Prevents NF Btranslocation and protects endothelial cell from senescence induced by uremia.Journals of Gerontology,2015,70:1198-1209.
15 De Sliva PM,Mohammed Abdul KS,Eakanayake EM,et al.Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology(CKDu)among Agricultural Communities in Sri Lanka.Plos Neglected Tropical Diseases,2016,10:e0004979.
16郭露露,赵卫红.NGAL与肾脏疾病研究进展.中华肾脏病杂志,2015,31:156-160.
17 Vohr HW.Monocyte Chemoattractant Protein 1(MCP-1).Cytokine,2016,60:1-12.
18 Jeon HJ,Choi HJ,Park BH,et al.Association of monocyte chemoattractant protein-1(MCP-1)2518A/G polymorphism with proliferative diabetic retinopathy in Korean type 2 diabetes.Yonsei Medical Journal,2013,54:621-625.
19高巍,武忠,李敏州,等.中医药基于TGF-β1治疗糖尿病肾病研究概况.中医药临床杂志,2017,29:164-167.
20 Jazi MF,Biglari A,Mazloomzadeh S,et al.Recombinant fibromodulin has therapeutic effects on diabetic nephropathy by down-regulating transforming growth factor-β1 in streptozotocin-induced diabetic rat model.Iranian Journal of Basic Medical Sciences,2016,19:265-271.
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