[1]王亚楠,朱晓楠,魏 箐.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[J].现代检验医学杂志,2024,39(06):79-83.[doi:10.3969/j.issn.1671-7414.2024.06.013]
　WANG Ya,nan,ZHU Xiaonan,et al.Correlation between the Expression of Neutrophil Extracellular Traps Markers cfDNA, CitH3 and MPO-DNA in Patients with T2DM and the Degree of Retinopathy[J].Journal of Modern Laboratory Medicine,2024,39(06):79-83.[doi:10.3969/j.issn.1671-7414.2024.06.013]
点击复制

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()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年06期
页码:
79-83
栏目:
论著
出版日期:
2024-11-15

文章信息/Info

Title:
Correlation between the Expression of Neutrophil Extracellular Traps Markers cfDNA, CitH3 and MPO-DNA in Patients with T2DM and the Degree of Retinopathy
文章编号:
1671-7414（2024）06-079-05
作者:
王亚楠; 朱晓楠; 魏 箐
（河南科技大学第一附属医院眼科，河南洛阳 471000）
Author(s):
WANG Ya; nan; ZHU Xiaonan; WEI Jing
（Department of Ophthalmology，the First Affiliated Hospital of Henan University of Science and Technology, Henan Luoyang 471000，China）
关键词:
2 型糖尿病; 糖尿病视网膜病变; 中性粒细胞外陷阱; 循环游离DNA; 瓜氨酸化组蛋白3; 髓过氧化物酶DNA
分类号:
R587.2；R774.1；R392.11
DOI:
10.3969/j.issn.1671-7414.2024.06.013
文献标志码:
A
摘要:
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 extracellulartraps，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（diabeticretinopathy，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。
Abstract:
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 MPODNA 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.

参考文献/References:

[1] LIN Kuanyu, HSIH W H, LIN Y B, et al. Update in the epidemiology, risk factors, screening, and treatment of diabetic retinopathy[J]. Journal of Diabetes Investigation, 2021, 12(8): 1322-1325.
[2] 张劲, 明媚. 增生性糖尿病视网膜病变患者玻璃体?房水和血浆中VEGF 表达与IL-6,IL-8 和TNF-α水平的相关性研究[J]. 现代检验医学杂志, 2021,36(4): 55-59. ZHANG Jin, MING Mei. Correlation of VEGF expression with IL-6, IL-8 and TNF-α levels in vitreous body, aqueous humor and plasma of patients with proliferative diabetic retinopathy[J]. Journal of Modern Laboratory Medicine, 2021, 36(4): 55-59.
[3] 冀帅飞, 宁小娜, 张婕. 中性粒细胞- 淋巴细胞比值在糖尿病视网膜病变诊断中的意义:Meta 分析[J].眼科, 2018, 27(6): 442-446. JI Shuaifei, NING Xiaona, ZHANG Jie. Neutrophil to lymphocyte ratio for diagnosis of diabetic retinopathy: a meta-analysis[J]. Ophthalmology in China, 2018,27(6): 442-446.
[4] BEREZIN A. Neutrophil extracellular traps: the core player in vascular complications of diabetes mellitus[J]. Diabetes & Metabolic Syndrome, 2019, 13(5): 3017-3023.
[5] 杨硕菲, 陈亮, 王浙宇, 等. 中性粒细胞陷阱网对糖尿病足临床愈合结局的预测价值[J]. 中国临床医学,2023, 30(1): 24-30. YANG Shuofei, CHEN Liang, WANG Zheyu, et al. Predictive value of neutrophil extracellular traps for clinical healing outcome of diabetic foot ulcer[J]. Chinese Journal of Clinical Medicine, 2023, 30(1): 24-30.
[6] WAN Wencui, LIU Hongzhuo, LONG Yang, et al. The association between circulating neutrophil extracellular trap related biomarkers and retinal vein occlusion incidence: a case-control pilot study[J]. Experimental eye research, 2021, 210: 108702.
[7] 中华医学会糖尿病学分会. 中国2 型糖尿病防治指南(2020 年版)[J]. 中华糖尿病杂志, 2021, 13(4):315-409. Chinese Diabetes Society, Chinese Medical Association. Guideline for the prevention and treatment of type 2 diabetes mellitus in China(2020 edition)[J]. Chinese Journal of Diabetes, 2021, 13(4): 315-409.
[8] 中华医学会眼科学分会眼底病学组. 中国医师协会眼科医师分会眼底病学组. 我国糖尿病视网膜病变临床诊疗指南(2022 年)[J]. 中华眼底病杂志, 2023,39(2): 99-124. Fundus Disease Group of Ophthalmological Society of Chinese Medical Association,Fundus Disease Group of Ophthalmologist Branch of Chinese Medical Doctor Association.Evidence-based guidelines for diagnosis and treatment of diabetic retinopathy in China(2022) [J]. Chinese Journal of Ocular Fundus Diseases, 2023,39(2): 99-124.
[9] 中华医学会眼科学会眼底病学组. 我国糖尿病视网膜病变临床诊疗指南(2014 年)[J]. 中华眼科杂志,2014, 50(11): 851-865. Fundus Disease Group of Ophthalmology Society of Chinese Medical Association. Evidence-based guidelines for diagnosis and treatment of diabetic retinopathy in China(2014)[J]. Chinese Journal of Ophthalmology, 2014, 50(11): 851-865.
[10] KLOPF J, BROSTJAN C, EILENBERG W, et al. Neutrophil extracellular traps and their implications in cardiovascular and inflammatory disease[J]. International Journal of Molecular Sciences, 2021,22(2): 559.
[11] 金忆瀛, 李玲, 厉平. 中性粒细胞细胞外陷阱及其抑制剂SerpinB1 与2 型糖尿病的关系[J]. 中国医师杂志, 2020, 22(9): 1438-1440, F0003. JIN Yiying, LI Ling, LI Ping. Relationship between neutrophil extracellular trap and its inhibitor serpinb1 and type 2 diabetes mellitus[J]. Journal of Chinese Physician, 2020, 22(9): 1438-1440, F0003.
[12] 郑桂莲, 耿晓慧, 张莎莎, 等. 中性粒细胞胞外陷阱?炎性蛋白水平对全膝关节置换术后下肢深静脉血栓形成预测价值分析[J]. 安徽医药, 2022, 26(6): 1128-1132. ZHENG Guilian, GENG Xiaohui, ZHANG Shasha,et al. Analysis of the predictive value of neutrophil extracellular traps and inflammatory protein levels for lower extremity deep vein thrombosis after total knee arthroplasty[J]. Anhui Medical and Pharmaceutical Journal, 2022, 26(6): 1128-1132.
[13] BASYREVA L Y, SHMELEVA E V, IVANOV V A, et al. The effect of vitamin D3 on neutrophil extracellular trap formation in high-glucose conditions[J]. Bulletin of Experimental Biology and Medicine, 2023, 176(2): 137-142.
[14] 陈加玉, 滕岩, 杨明明. 炎症调控因子在糖尿病视网膜病变新生血管形成中的作用[J]. 国际眼科杂志,2021, 21(8): 1390-1393. CHEN Jiayu, TENG Yan, YANG Mingming. Role of inflammatory regulators in neovascularization of diabetic retinopathy[J]. International Eye Science,2021, 21(8): 1390-1393.
[15] MART?NEZ-ALBERQUILLA I, GASULL X, P?REZLUNA P, et al. Neutrophils and neutrophil extracellular trap components: Emerging biomarkers and therapeutic targets for age-related eye diseases[J]. Ageing Research Reviews, 2022, 74: 101553.
[16] 庄宪丽, 张莹, 杨家干, 等. 基于VEGF-VEGFR 通路探究Avastin 对DR 模型大鼠干预效果[J]. 中国老年学杂志, 2023, 43(4): 955-959. ZHUANG Xianli, ZHANG Ying, YANG Jiagan, et al. Explore the intervention effect of Avastin on DR model rats based on VEGF-VEGFR pathway[J]. Chinese Journal of Gerontology, 2023, 43(4): 955-959.
[17] WANG Luo ziyi, ZHOU Xin, YIN Yizhou, et al. Hyperglycemia induces neutrophil extracellular traps formation through an NADPH oxidase-dependent pathway in diabetic retinopathy[J]. Frontiers in Immunology, 2018, 9: 3076.
[18] 王罗梓怡. 高糖诱导中性粒细胞胞外陷阱在糖尿病性视网膜病变中的作用机制研究[D]. 重庆:重庆医科大学, 2019:1-53. WANG Luoziyi . Hyperglycemia induces neutrophil extracelliular traps formation through an NADPH oxidase-dependent pathday in diabetic retinopathy[D]. Chongqing: Chongqing Medical University , 2019:1-53.
[19] MAGA?A-GUERRERO F S, AGUAYO-FLORES J E, BUENTELLO-VOLANTE B, et al. Spontaneous neutrophil extracellular traps release are inflammatory markers associated with hyperglycemia and renal failure on diabetic retinopathy[J]. Biomedicines, 2023,11(7): 1791.

相似文献/References:

[1]韩登科,房绮梅,谢晋烨,等.2 型糖尿病并发高血压患者血清Fetuin B 水平检测及与Hcy 浓度的相关性研究[J].现代检验医学杂志,2020,35(02):24.[doi:10.3969 ／ j.issn.1671-7414.2020.02.008]
　HAN Deng-ke,FANG Qi-mei,XIE Jin-ye,et al.Serum Fetuin B Level in Patients with Type 2 Diabetes Mellitus Complicated withHypertension and Its Correlation with Hcy Concentration were Investigated[J].Journal of Modern Laboratory Medicine,2020,35(06):24.[doi:10.3969 ／ j.issn.1671-7414.2020.02.008]
[2]刘肖瑛,林佩娜,欧阳伟庆,等.2 型糖尿病患者血清sdLDL 和脂类水平及相关性分析[J].现代检验医学杂志,2020,35(03):58.[doi:10.3969/j.issn.1671-7414.2020.03.014]
　LIU Xiao-ying,LIN Pei-na,OUYANG Wei-qing,et al.Analysis of Serum sdLDL and Lipid Levels and Their Correlation in Patients with Type 2 Diabetes[J].Journal of Modern Laboratory Medicine,2020,35(06):58.[doi:10.3969/j.issn.1671-7414.2020.03.014]
[3]洪雄新,李观强,杨 辉,等.2 型糖尿病患者ABCA1 R219K 基因多态性分布及其与血脂水平的相关性研究[J].现代检验医学杂志,2020,35(04):14.[doi:10.3969/j.issn.1671-7414.2020.04.004]
　HONG Xiong-xin,LI Guan-qiang,YANG Hui,et al.Study on Distribution of ABCA1 R219K Gene Polymorphism and Its Correlation with Blood Lipid Levels for Type 2 Diabetes Mellitus Patients[J].Journal of Modern Laboratory Medicine,2020,35(06):14.[doi:10.3969/j.issn.1671-7414.2020.04.004]
[4]骆时木,叶宇宸,欧阳航,等.福建省泉州地区汉族人群TCF7L2 rs11196205基因多态性与T2DM 的相关性研究[J].现代检验医学杂志,2020,35(04):22.[doi:10.3969/j.issn.1671-7414.2020.04.006]
　LUO Shi-mu,YE Yu-chen,OUYANG Hang,et al.Correlation between TCF7L2 rs11196205 Gene Polymorphism and Onset Risk of T2DM in Han Population of Quanzhou, Fujian Province[J].Journal of Modern Laboratory Medicine,2020,35(06):22.[doi:10.3969/j.issn.1671-7414.2020.04.006]
[5]杨莉婷,陈 翠,蒋兴亮.2 型糖尿病患者血清残余胆固醇水平与超敏C 反应蛋白表达的相关性研究[J].现代检验医学杂志,2020,35(04):45.[doi:10.3969/j.issn.1671-7414.2020.04.011]
　YANG Li-ting,CHEN Cui,JIANG Xing-liang.Association between Serum Remnant Cholesterol Levels and Expression of High Sensitive C-reactive Protein in Patients with Type 2 Diabetes Mellitus[J].Journal of Modern Laboratory Medicine,2020,35(06):45.[doi:10.3969/j.issn.1671-7414.2020.04.011]
[6]张海霞a,郭 杰a,袁 宁a,等.老年健康体检人群外周血红细胞分布宽度与糖化血红蛋白A1c 的相关性研究[J].现代检验医学杂志,2020,35(04):65.[doi:10.3969/j.issn.1671-7414.2020.04.016]
　ZHANG Hai-xia a,GUO Jiea,YUAN Ninga,et al.Association of Peripheral Blood Red Blood Cell Distribution Width with Glycated Hemoglobin A1c in the Healthy Elderly Population for Check-ups[J].Journal of Modern Laboratory Medicine,2020,35(06):65.[doi:10.3969/j.issn.1671-7414.2020.04.016]
[7]张 艳a,刘 翔a,李鸿钏a,等.血清脂蛋白磷脂酶A2 和血浆抗凝血酶Ⅲ对2 型糖尿病患者发生缺血性脑卒中风险的评估价值[J].现代检验医学杂志,2020,35(04):71.[doi:10.3969/j.issn.1671-7414.2020.04.017]
　ZHANG Yana,LIU Xianga,LI Hong-chuana,et al.Evaluation Value of Serum Lipoprotein-Associated Phospholipase A2 and Plasma Antithrombin Ⅲ on the Risk of Ischemic Stroke in Patients with Type 2 Diabetes Mellitus[J].Journal of Modern Laboratory Medicine,2020,35(06):71.[doi:10.3969/j.issn.1671-7414.2020.04.017]
[8]张 凯,李全双,程 星.2 型糖尿病患者血清低清蛋白水平对糖化清蛋白检测结果的影响[J].现代检验医学杂志,2020,35(04):126.[doi:10.3969/j.issn.1671-7414.2020.04.032]
　ZHANG Kai,LI Quan-shuang,CHENG Xing.Effect of Serum Low Albumin Level on the Detection of Glycosylated Albumin in Patients with Type 2 Ddiabetes Mellitus[J].Journal of Modern Laboratory Medicine,2020,35(06):126.[doi:10.3969/j.issn.1671-7414.2020.04.032]
[9]刘倩倩,鲁作华,王 星,等.血浆D- 二聚体在2 型糖尿病患者早期肾损伤中的应用价值[J].现代检验医学杂志,2020,35(04):134.[doi:10.3969/j.issn.1671-7414.2020.04.034]
　LIU Qian-qian,LU Zuo-hua,WANG Xing,et al.Application Value of Serum D-Dimer in Early Kidney Injury in Patients with Type 2 Diabetes[J].Journal of Modern Laboratory Medicine,2020,35(06):134.[doi:10.3969/j.issn.1671-7414.2020.04.034]
[10]欧阳清慧,王 冰,杨自力,等.四川省绵阳地区慢性丙型肝炎患者继发2 型糖尿病危险因素分析[J].现代检验医学杂志,2020,35(04):151.[doi:10.3969/j.issn.1671-7414.2020.04.038]
　OUYANG Qing-hui,WANG Bing,YANG Zi-li,et al.Analysis of Risk factors of Chronic Hepatitis C Complicated with Type 2 Diabetes Mellitus in Mianyang of Sichuan[J].Journal of Modern Laboratory Medicine,2020,35(06):151.[doi:10.3969/j.issn.1671-7414.2020.04.038]

备注/Memo

备注/Memo:
作者简介：王亚楠（1994-），男，硕士在读，住院医师，研究方向：眼底病，E-mail：ranbu026@163.com。
通讯作者：魏箐（1973-），女，博士，主任医师，E-mail：wj18567635881@163.com。
更新日期/Last Update: 2024-11-15