2型糖尿病患者血浆中NETs标志物cfDNA,CitH3和MPO-DNA表达水平与视网膜病变程度相关性研究

Correlation between the Expression of Neutrophil Extracellular Traps Markers cfDNA,CitH3 and MPO-DNA in Patients with T2DM and the Degree of Retinopathy

目的探讨2型糖尿病(type 2 diabetes mellitus,T2DM)患者血浆中性粒细胞外陷阱(neutrophil extracellular traps,NETs)标志物循环游离DNA(circulating free DNA,cfDNA)、髓过氧化物酶(myeloperoxidase,MPO)-DNA、瓜氨酸化组蛋白3(citrullinated histone 3,CitH3)表达水平与视网膜病变程度的相关性。方法选取2023年1~9月河南科技大学第一附属医院80例T2DM患者为研究对象,依据T2DM患者视网膜病变情况分为无糖尿病视网膜病变(non-diabetic retinopathy,NDR)组(n=30)、非增生型糖尿病视网膜病变(nonproliferative diabetic retinopathy,NPDR)组(n=26)和增生型糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)组(n=24)。收集入选患者一般资料,检测血浆cfDNA,MPO-DNA及CitH3水平;采用Spearman相关性分析cfDNA,CitH3,MPO-DNA与T2DM患者视网膜病变严重程度的关系;ROC曲线分析cfDNA,CitH3,MPO-DNA及联合预测T2DM患者糖尿病视网膜病变(diabetic retinopathy,DR)发生的效能。结果NDR组、NPDR组和PDR组cfDNA(65.13±18.28,83.34±20.10,114.52±32.36ng/ml),CitH3(17.76±4.24,22.03±5.01,26.06±8.13 ng/ml),MPO-DNA(0.31±0.04,0.35±0.05,0.45±0.05)水平依次升高,差异具有统计学意义(F=28.755,13.335,62.470,均P<0.001);其中PDR组、NPDR组cfDNA,CitH3,MPO-DNA水平均高于NDR组(t=7.076,4.837,11.436;3.550,3.455,3.324),且PDR组cfDNA,CitH3,MPODNA水平高于NPDR组(t=4.127,2.128,7.065),差异具有统计学意义(均P<0.05)。Spearman相关性分析显示,cfDNA,CitH3,MPO-DNA与T2DM患者视网膜病变严重程度均呈正相关(r=0.659,0.470,0.744,均P<0.001)。ROC曲线显示,cfDNA,CitH3,MPO-DNA及联合检测曲线下面积[AUC(95%CI)]分别为0.846(0.758~0.934),0.776(0.674~0.878),0.847(0.764~0.930)和0.938(0.889~0.987),对于T2DM患者发生DR具有一定预测价值。结论DR患者血浆中NETs标志物cfDNA,MPO-DNA及CitH3水平升高,其水平与DR程度呈正相关,一定程度上可预测T2DM患者DR的发生情况,且联合预测价值最高。

Objective To explore the correlation between the expression levels of neutrophil extracellular traps(NETs)markers circulating free DNA(cfDNA),citrullinated histone 3(CitH3),myeloperoxidase(MPO)-DNA in plasma and the degree of retinopathy in patients with type 2 diabetes mellitus(T2MD).Methods A sum of 80 patients with type 2 diabetes mellitus(T2DM)in First Affiliated Hospital of Henan University of Science and Technology from January to September 2023 were selected as the study objects.According to the retinopathy of T2DM patients,they were divided into non-diabetic retinopathy(NDR)group(n=30),nonproliferative diabetic retinopathy(NPDR)group(n=26)and proliferative diabetic retinopathy(PDR)group(n=24).General data of enrolled patients were collected and plasma cfDNA,CitH3,MPO-DNA levels were detected.Spearman correlation was used to analyze the relationship between cfDNA,CitH3,MPO-DNA and the severity of retinopathy in T2DM patients.ROC curves were used to analyze the efficacy of cfDNA,CitH3,MPO-DNA and their combination in predicting the occurrence of diabetic retinopathy(DR)in T2DM patients.Results The levels of cfDNA(65.13±18.28,83.34±20.10,114.52±32.36 ng/ml),CitH3(17.76±4.24,22.03±5.01,26.06±8.13 ng/ml)and MPO-DNA(0.31±0.04,0.35±0.05,0.45±0.05)in NDR group,NPDR group and PDR group were increased successively,and the differences were statistically significant(F=28.755,13.335,62.470,all P<0.001).The levels of cfDNA,CitH3 and MPO-DNA in PDR group and NPDR group were higher than those in NDR group(t=7.076,4.837,11.436;3.550,3.455,3.324),and the levels of cfDNA,CitH3,and MPO-DNA in PDR group were higher than those in NPDR group(t=4.127,2.128,7.065),and the differences were statistically significant(all P<0.05).Spearman correlation analysis showed that cfDNA,CitH3 and MPO-DNA were positively correlated with the severity of retinopathy in T2DM patients(r=0.659,0.470,0.744,all P<0.001).ROC curves showed that the AUC(95%CI)of cfDNA,CitH3,MPO-DNA and combined detection were 0.846(0.758~0.934),0.776(0.674~0.878),0.847(0.764~0.930)and 0.938(0.889~0.987),respectively,and it had certain predictive value for DR in T2DM patients.Conclusion The levels of NETs markers cfDNA,MPO-DNA and CitH3 in the plasma of DR Patients are increased,and their levels are positively correlated with the degree of diabetic retinopathy,which can predict the occurrence of DR in T2DM patients to a certain extent,and the combined prediction value is the highest.