目的 探讨血清高迁移率族蛋白B1(HMGB1)、胰岛素样生长因子1(IGF-1)和血管内皮生长因子165(VEGF 165)水平与糖尿病肾病(DN)病情进展的相关性.方法 选择2016年1月至2018年1月在南京医科大学附属淮安第一医院被确诊为DN的136例患者(DN组)为研究对象,其中微量蛋白尿组62例、大量蛋白尿组50例、肾功能损害组24例.选择同期健康体检者115例作为健康对照组.检测所有受试者空腹血糖、血总胆固醇、血三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和尿白蛋白/肌酐比值.采用酶联免疫吸附法(ELASA)检测血清HMGB1、IGF-1及VEGF165浓度.应用Pearson相关分析分析血清HMGB1、IGF-1与VEGF 165间的相关性;Logistic有序多分类回归分析DN病情进展的危险因素;并绘制受试者工作特征曲线(ROC),评估HMGB1、IGF-1与VEGF165在DN病情进展中的预测价值.结果 DN组患者血清HMGB1、IGF-1和VEGF165水平明显高于健康对照组(均P＜0.01).Pearson相关分析结果显示,DN组患者血清HMGB1、IGF-1及VEGF165水平与尿白蛋白/肌酐比值呈正相关(均P＜ 0.01);血清HMGB1与IGF-1、HMGB1与VEGF165、IGF-1与VEGF165间均呈正相关(P＜0.01).Logistic回归分析结果显示,HMGB1、IGF-1和VEGF165水平升高是DN病情进展的独立危险因素(OR值分别为5.50、1.05、1.24,均P＜0.05).HMGB1、IGF-1和VEGF165检测联合诊断DN病情进展的敏感性、特异性和ROC曲线下面积均高于单独检测的诊断效果(曲线下面积分别为0.989、0.984、0.942、0.878,P ＜ 0.05).结论 血清HMGB1、IGF-1和VEGF165水平与DN病情严重程度相关,HMGB1、IGF-1和VEGF165联合诊断对DN病情进展的临床预测价值优于HMGB1、IGF-1和VEGF165单一指标.%Objectives To determine the association between serum levels of high-mobility group box-1 (HMGB1),insulin-like growth factor-1 (IGF-1),vascular endothelial growth factor 165 (VEGF165) and occurrence and development of diabetic nephropathy (DN).Methods A total of 136 patients diagnosed as diabetic nephropathy (DN group) in Huai'an First People's Hospital between January 2016 to January 2018 were randomly selected in the study,including microalbuminuria group (n=62),macroalbuminuria group (n=50) and renal insufficiency group (n=24).Meanwhile,115 healthy examiners during the same period were collected as normal control group.Serum glucose,serum total cholesterol (TC),serum triglyceride (TG),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C) and urinary albumin/urine creatinine ratio (UAlb/Cr) were detected inall subjects.Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the serum concentrations of HMGB1,IGF-1 and VEGF165.Pearson correlation test was used to analyze the correlation between serum HMGB1,IGF-1 and VEGF165.Logistic ordered multi-classification regression was used to analyze the risk factors of DN progression,and the receiver operating characteristic curve (ROC) was drawn to evaluate the clinical predictive value of HMGB1,IGF-1 and VEGF165 in the progression of DN.Results The concentrations of serum HMGB1,IGF-1 and VEGF165 in DN patients were significantly higher than those in the control group (all P ＜ 0.05).There was a positive association between HMGB1 and IGF-1,HMGB1 and VEGF165,IGF-1 and VEGF165 (all P ＜ 0.01).Logistic regression analysis showed that elevated levels of HMGB1,IGF-1 and VEGF165 were independent risk factors for DN progression (OR=5.50,1.05,1.24,all P ＜ 0.05).The sensitivity,specificity and area under ROC curve of combined detection of HMGB1,IGF-1 and VEGF165 were higher than HMGB1,IGF-1 and VEGF165 alone (AUC=0.989,0.984,0.942,0.878,P ＜ 0.05).Conclusions The serum levels of HMGB1,IGF-1 and VEGF165 are related to the severity of DN.The clinical predictive value of combined detection of HMGB1,IGF-1 and VEGF165 for DN progression is superior to that of single index detection of HMGB1,IGF-1 and VEGF165.
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