| Objective: Diabetic kidney disease(DKD)is one of the main chronic microvascular diseases in diabetes.The pathogenesis of DKD is complicated,which is closely related to multiple factors such as the onset time,glucose metabolism disorder,renal hemodynamic changes and heredity.Plasminogen activator inhibitor-1(PAI-1),which is synthesized by vascular endothelial cells,megakaryocytes and hepatocytes,has a certain inhibitory effect on the fibrinolytic system physiologically.When the extra cellular matrix(ECM)is damaged,its ability to synthesize t-PA is decreased and the expression of PAI-1 gradually increases,resulting in the breakdown of fibrinolytic balance,accumulation and proliferation of glomerular ECM and the decrease of glomerular filtration rate.The high level blood glucose stimulates the expression of oxygen free radicals significantly.The level of oxidative stress increases results in fibrosis of the local tissues of the kidney,disturbance of the internal matrix and promoting the occurrence of diabetic kidney disease.Nuclea factor erythroid-2-related factor2(Nrf2),the most sensitive factor of antioxidant stress,plays an important role in the antioxidant stress process.When the Nrf2/anti-oxidative response element(ARE)signal pathway is activated,the kidney's ability to resist oxidative stress is enhanced,and extracellular matrix deposition is reduced,thus protecting the kidney from damage.The purpose of this study were to investigate the changes of PAI-1 and Nrf2 in patients with simple diabetes and patients with diabetic kidney disease and to explore the values in the early diagnosis and the pathogenesis of diabetic kidney disease.Methods: A total of 167 patients with type 2 diabetes were selected from the department of endocrinology,the first central hospital of Baoding city,Hebei province.According to urine albuminuria/creatinine ratio(UACR),these subjects were divided into T2 DM 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 general data of the research subjects were collected,and the fasting blood glucose(FBG),serum index,urine index,and serum PAI-1 and Nrf2 levels were measured in each group.The content of PAI-1,Nrf2 and clinical indicators were compared by one-way ANOVA.Spearman correlation analysis was used to analyze the correlation between serum PAI-1 and Nrf2 and various influencing factors.To explore the role of PAI-1 and Nrf2 in the development of DKD,logistic regression analysis were used to analyze the effects of serum PAI-1 and Nrf2 and many other factors on diabetic kidney disease.ROC curve was used to evaluate the predictive value of PAI-1 and Nrf2 in the diagnosis and severity of DKD.P< 0.05 had statistical significance.Results: 1.Compared to NC group,the serum PAI-1 level of DM group,DKD1 group and DKD2 group increased successively(P < 0.05)(78.55±20.66?87.18±12.9?99.40±5.31 vs 67.72±20.39ng/L)and the serum Nrf2 gradually decreased(P < 0.05)(1.41±0.32?1.24±0.24?0.98±0.2 vs 1.65±0.37ng/L);2.Compared to DM group,UALB,UAER and UACR levels in DKD1 group and DKD2 group increased successively,with the highest level in DKD2 group(P < 0.05).The 24 h urine protein in DKD2 group was significantly higher than that in DM group(P < 0.05);3.Serum PAI-1 was positively correlated with the course of diabetes,FBG,Hb A1 c,INS,HOMA-IR,SCR,UALB,UAER,UACR and 24 h urine protein,and negatively correlated with ALB and Nrf2(P < 0.05);4.Serum Nrf2 was positively correlated with TP and ALB,and negatively correlated with BMI,FBG,Hb A1 c,HOMA-IR,BUN,SCR,UALB,UAER,UACR,24 h urine protein and PAI-1(P < 0.05);5.Logistic regression analysis showed that Hb A1 c,UACR and PAI-1 were risk factors of DKD and Nrf2 was a protective factor of DKD;6.ROC curve analysis showed that the AUC of serum PAI-1 in the diagnosis of DKD was 0.818(95%CI 0.758 ? 0.879,P < 0.01),the optimal threshold was 75.295 ng/L,and the sensitivity and specificity were 91.70% and 62.10%.The AUC of Nrf2 in diagnosing DKD was 0.802(95%CI 0.745 ? 0.860,P < 0.01),the optimal threshold was 1.086 ng/L,and the sensitivity and specificity were 62.30% and 89.20%.7.The AUC of serum PAI-1 for diagnosis of DKD2 group was 0.814(95%CI 0.736 ? 0.892,P < 0.01),the optimal threshold was 95.20 ng/L,and the sensitivity and specificity were 88.80% and 66.10%.The AUC of Nrf2 was 0.766(95%CI 0.677 ? 0.856,P < 0.01),the optimal threshold was 0.926 ng/L,and the sensitivity and specificity were 68.20% and 80.10%.Conclusion:1.Serum levels of PAI-1 were increased and the Nrf2 were decreased in patients with simple type 2 diabetes and diabetic kidney disease.As the increase of UACR level,there were distinct augment trend of PAI-1 and downtrend of Nrf2 in patients with type 2 diabetic kidney disease.2.Serum PAI-1 and Nrf2 levels were related to blood glucose control and urinary protein excretion,suggesting that two factors may affect urinary protein excretion and affect the occurrence and development of diabetic kidney disease.3.Hb A1 c,UACR,PAI-1 were risk factors for kidney disease in patients with type 2 diabetes,while Nrf2 reduces the occurrence and development of diabetic kidney disease was a protective factor.4.It had been proved that serum PAI-1 and Nrf2 had certain value analysis in the evaluation of type 2 diabetic kidney disease.The sensitivity of serum PAI-1 was high and the specificity of serum Nrf2 was high,which would provide basis for future clinical research. |
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