2型糖尿病不同尿白蛋白排泄率患者血清Sirt1与炎症因子的相关关系

The relationship between serum Sirt1 and EGR1 and other inflammatory cytokines in type 2 diabetic patients with different stages of diabetic nephropathy

目的 探讨2型糖尿病不同尿白蛋白排泄率患者血清沉默信息调节因子1（Sirt1）与炎症因子水平及其相关关系.方法 436例2型糖尿病患者根据尿白蛋白排泄率（尿白蛋白与尿肌酐的比值,ACR）分为正常蛋白尿组（D1组168例）、微量蛋白尿组（D2组152例）、临床蛋白尿组（D3组116例）.采用酶联免疫分析（ELISA）法检测血清Sirt1、低氧诱导因子-1α（HIF-1α）、生长应答蛋白1（EGR1）、胰岛素样生长因子-Ⅰ （ⅠGF-Ⅰ）、单核细胞趋化蛋白-1（MCP-1）水平.并与正常对照组180例相比较.结果 2型糖尿病患者血清Sirt1水平显著低于对照组,且随着尿白蛋白排泄率增加,D1、D2、D3组Sirt1水平逐渐降低（P＜0.01）.与对照组相比,2型糖尿病患者血清炎症因子（HIF-1α、EGR1、IGF-Ⅰ、MCP-1）水平显著升高,并在D1、D2、D3组逐渐升高（均P＜0.01）.且血清Sirt1与炎症因子水平呈负相关.尿白蛋白/尿肌酐比值对数值[Ln （ACR）]（ACR取自然对数）与年龄、DM病史、FBG、空腹胰岛素（FINS）、HOMA-IR、HbA1c、LDL、TC、TG、血肌酐（Scr）、血尿素氮（BUN）、尿酸（UA）、HIF-1α、EGR1、IGF-Ⅰ、MCP-1呈正相关（P＜0.05）;与Sirt1呈负相关（P＜0.01）.HIF-1α、MCP-1、IGF-Ⅰ、DM病史、BUN、Sirt1、UA、LDL以及EGR1是影响Ln （ACR）的主要因素（P＜0.05）.结论 血清Sirt1或成为糖尿病肾病治疗的新靶点.提高血清Sirt1水平可能具有延缓糖尿病肾病的作用.

Objective To investigate changes of serum silent information regulator 1 （Sirt1） and inflammatory cytokines in type 2 diabetes patients with different stages of diabetic nephropathy.To explore the relationship between serum Sirt1 level and inflammatory cytokines in type 2 diabetic patients with different urinary albumin excretion rates.Methods A total of 436 cases with type 2 diabetes were divided into three groups：normoalbuminuric [D1,n =168],microalbuminuric [D2;n =152],and macroalbuminuric [D3,n =116].Serum Sirt1,hypoxia-inducible factor-1α （HIF-1α）,early growth response protein 1 （EGR1）,insulin-like growth factors-Ⅰ （IGF-Ⅰ）,and monocyte chemotactic protein-1 （MCP-1） were determined by enzyme-linked immunosorbent assay （ELISA）.Results The levels of serum Sirt1 in type 2 diabetes patients were significantly lower than that in control group,and with the increase of urinary protein excretion rate,the levels of serum Sirt1 in group D1,D2 and D3 were decreased gradually （P 〈 0.01）.Compared to control,serum inflammatory cytokines （HIF-1α,EGR1,IGF-Ⅰ,and MCP-1） levels were significantly increased in type 2 diabetic patients and gradually increased in the patients of D1,D2 and D3 groups （P 〈0.01）.Furthermore,Serum Sirt1 was negatively correlated with the levels of inflammatory cytokines.Age,duration,fasting blood glucose （FBG）,fasting insulin （FINS）,homeostasis model assessment insulin resistance index （HOMA-IR）,glycosylated hemoglobin （HbA1c）,low density lipoprotein （LDL）,total cholesterol （TC）,triglyceride （TG）,serum creatinine （Scr）,blood urea nitrogen （BUN）,uric acid （UA）,HIF-1α,EGR1,IGF-Ⅰ,and MCP-1 were positively correlated with Ln Koc of urinary albumin to creatinine ratio [Ln（ACR）] （P 〈 0.05）;and Sirt1 were negatively correlated with Ln（ACR）（P 〈 0.01）.HIF-1α,MCP-1,IGF-Ⅰ,duration,BUN,Sirt1,UA,LDL,and EGR1 were independent factors that significantly influenced Ln （ACR） （P 〈 0.05）.Conclusions Serum Sirt1 might be a new target for the treatment of diabetic nephropathy.Enhancing serum Sirt1 levels might have a role in delaying the progression of diabetic nephropathy.