2型糖尿病肾病患者血浆纤溶酶原激活物抑制剂1及核因子E2相关因子2水平变化及临床意义

Changes and significance of serum plasminogen activator inhibitor-1 and nuclea factor erythroid-2-related factor2 in patients of type 2 diabetic kidney disease

目的分析在2型糖尿病肾病(DKD)患者中血浆纤溶酶原激活物抑制剂1(PAI-1)及核因子E2相关因子2(Nrf2水平的变化及意义。方法选取2019年10月~2020年12月保定市第一中心医院内分泌科收治的2型糖尿病患者167例,根据尿白蛋白/肌酐比值(UACR)分为单纯2型糖尿病组(DM组,n=58),微量蛋白尿组(DKD1组,n=59),大量蛋白尿组(DKD2组,n=50),并选取同期体检健康人群为健康对照组(NC组,n=45)。测定各组PAI-1及Nrf2水平。采用Spearman相关分析法及logistic回归分析法分析PAI-1及Nrf2与各影响因素之间的相关性及评估DKD的影响因素。采用受试者工作特征曲线(ROC)评估PAI-1及Nrf2对DKD的诊断价值。结果与NC组相比,DM组、DKD1组及DKD2组PAI-1水平依次升高,Nrf2水平依次下降,以DKD2组最显著,差异有统计学意义(P<0.05)。Spearman相关分析结果显示,PAI-1与糖尿病病程、空腹血糖、糖化血红蛋白、肌酐、UACR及24 h尿蛋白呈正相关,与白蛋白、Nrf2呈负相关(P<0.05);Nrf2与白蛋白呈正相关,与空腹血糖、糖化血红蛋白、肌酐、UACR、24 h尿蛋白及PAI-1呈负相关(P<0.05)。Logistic回归分析显示HbA1c、UACR及PAI-1为DKD的危险因素,Nrf2为DKD的保护因素。血清PAI-1及Nrf2诊断糖尿病肾病的ROC曲线下面积分别为0.818及0.802。结论糖尿病肾病患者血浆PAI-1和Nrf2与尿白蛋白有较强相关性。抑制PAI-1、提高Nrf2可能成为治疗糖尿病肾病的新靶点。

Objective To analyze the changes and the clinical values of serum PAI-1 and Nrf2 in patients of type 2 diabetic kidney disease.Methods A total of 167 patients with type 2 diabetes were selected from our hospital.According to UACR,these subjects were divided into T2DM without proteinuria group(DM group,n=58),the microalbuminuria group(DKD1 group,n=59),and the macroalbuminuria group(DKD2 group,n=50).Meanwhlie,healthy adults who underwent physical examination during the same period were selected as the control group(NC group,n=45).The clinical data of all subjects were collected,and enzyme-linked immunosorbent assay was used to determine and compare the levels of PAI-1 and Nrf2 between groups.Spearman correlation analysis was used to analyze the correlation between PAI-1 and Nrf2 and various influencing factors.Logistic regression analysis was used to to evaluate the influencing factors of DKD.The ROC curve was used to evaluate the early predictive value of PAI-1 and Nrf2 for DKD.Results Compared with NC group,the PAI-1 level increased and the Nrf2 level decreased sequentially in the DM group,the DKD1group and the DKD2 group,with the DKD2 group being the most significant(P<0.05).Spearman correlation analysis showed that PAI-1 was positively correlated with diabetes course,fasting venous blood glucose,glycosylated hemoglobin,creatinine,UACR and24h urine protein,and negatively correlated with albumin and Nrf2(P<0.05).Nrf2 was positively correlated with albumin,and negatively correlated with fasting venous blood glucose,glycosylated hemoglobin,creatinine,UACR,24h urine protein and PAI-1(P<0.05).Logistic regression analysis showed that HbA1c,UACR and PAI-1 were risk factors of DKD and Nrf2 was a protective factor of DKD.The ROC curve showed that the area under the curve of PAI-1 and Nrf2 for predicting DKD was 0.818 and 0.802,respectively,suggesting that PAI-1 and Nrf2 can help predict DKD,and PAI-1 was more sensitive than Nrf2.Conclusion Diabetes PAI-1increased and Nrf2 decreased,and the amplitude of change is strongly correlated with urinary albumin level.Inhibiting PAI-1 and raising Nrf2 level may be a new target for treating diabetes nephropathy.