[1]张威 段高羊 郭瑶 唐明生 吴沣芝 蒋丰智.川崎病急性期中性粒细胞胞外诱捕网与血管损伤的相关研究[J].心血管病学进展,2024,(11):1046.[doi:10.16806/j.cnki.issn.1004-3934.2024.11.018]
 ZHANG Wei,DUAN Gaoyang,GUO Yao,et al.A Preliminary Study of the Involvement of Neutrophil Extracellular Traps on Vascular Injury in the Acute Phase of Kawasaki Disease[J].Advances in Cardiovascular Diseases,2024,(11):1046.[doi:10.16806/j.cnki.issn.1004-3934.2024.11.018]
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川崎病急性期中性粒细胞胞外诱捕网与血管损伤的相关研究()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2024年11期
页码:
1046
栏目:
论著
出版日期:
2024-11-25

文章信息/Info

Title:
A Preliminary Study of the Involvement of Neutrophil Extracellular Traps on Vascular Injury in the Acute Phase of Kawasaki Disease
作者:
张威1 段高羊2 郭瑶2 唐明生2 吴沣芝1 蒋丰智2
(1.广东医科大学研究生院第一临床学院,广东 湛江 524023;2.广东医科大学东莞市妇幼保健院儿科,广东 东莞 523112)
Author(s):
ZHANG Wei1DUAN Gaoyang2GUO Yao2TANG Mingsheng2WU Fengzhi1JIANG Fengzhi2
(1.The First Clinical School of Medicine,Graduate School of Guangdong Medical University,Zhanjiang 524023,Guangdong,China;2.Department of Pediatric,Dongguan Maternal and Child Health Care Hospital affiliated to Guangdong Medical University,Dongguan 523112,Guangdong,China) ()(20211800904762) E-mailfortunejam@163.com
关键词:
川崎病血管炎中性粒细胞胞外诱捕网内皮微粒血管性血友病因子血小板衍生微粒
Keywords:
Kawasaki disease Vasculitis Neutrophil extracellular traps Endothelial microparticles von Willebrand factor Platelet-derived microparticles Kawasaki diseaseKD19675[1]coronary artery lesionCALKDCAL[2]neutrophil extracellular trapsNETsNETosisKDNETs-
DOI:
10.16806/j.cnki.issn.1004-3934.2024.11.018
摘要:
目的 观察中性粒细胞胞外诱捕网(NETs)形成在川崎病(KD)急性期中的变化,探讨其参与KD血管损伤可能和相关药物的保护机制。方法 留取2022年1月—2023年6月东莞市妇幼保健院收治的40例KD患儿静脉注射丙种球蛋白前、后与对照组40例健康同龄儿童血样,对外周血中性粒细胞计数和酶联免疫吸附试验法检测血浆中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和循环游离DNA(cfDNA、LL-37、脱氧核糖核酸酶(DNase),以及血管性血友病因子(vWF)、内皮细胞微粒EMPs)及血小板衍生微粒PDMP)水平并进行分析。结果 KD急性期患儿外周血中中性粒细胞计数和TNF-α、以及NETs主要成分cfDNALL-37水平增高,DNase水平下降,丙种球蛋白治疗后恢复,且与对照组无统计学差异;同时血浆中、EMPsPDMP也均增高,丙种球蛋白治疗后下降,与对照组无统计学差异;有冠状动脉扩张者KD急性期的中性粒细胞计数、、cfDNA及、EMPs、PDMP较无冠状动脉扩张者高DNaseⅠ则较之低;相关分析提示,NETs主要成分cfNDA与EMPs、及PDMP水平呈正相关,与DNase水平呈负相关。结论 KD急性期存在NETs过表达和DNase降解能力下降与病情相关,动态监测cfDNA在早期诊断和病情严重程度评估中有一定临床价值;NETs可能参与了KD的血管炎症内皮损伤-凝血轴反应;提示丙种球蛋白通过减少NETs损伤途径发挥一定药理保护作用。
Abstract:
Objective To observe the changes of neutrophil extracellular traps (NETs) formation in the acute phase of Kawasaki disease (KD), and explore the possible involvement of NETs in KD vascular injury and the protective mechanism of related drugs. Methods Blood samples of 40 KD children treated in Dongguan Maternal and Child Health Care Hospital before and after intravenous immunoglobulin (IVIG) treatment and 40 healthy children of the same age as control group were collected during the period from January 2022 to June 2023. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6),circulating?cell-free DNA (cfDNA), LL-37, deoxyribonuclease I (DNaseⅠ), von Willebrand factor (vWF), endothelial microparticles (EMPs), platelet-derived microparticles (PDMP) in plasma detected by ELISA and peripheral blood neutrophil count of all the specimen were comparedand analyzed. Results In the acute phase of KD, neutrophil count, the level of TNF-α, IL-6, and cfDNA and LL-37 as main components of NETs increased and DNaseⅠ decreased, while those recovered after IVIG treatment, and there were no statistical difference compared with the control group. At the same time, vWF, EMPs and PDMP in plasma also increased, and decreased after treatment with IVIG, and there were no statistical difference compared with the control group. In the acute phase of KD, neutrophil count, TNF-α, cfDNA, vWF, EMPs and PDMP were higher in patients with coronary artery dilatation than those without coronary artery dilation, while DNaseⅠ was lower. Correlation analysis showed that cfNDA, the main component of NETs, was positively correlated with the concentration of EMPs, vWF and PDMP, and negatively correlated with DNaseⅠ. Conclusions NETs over-expression and DNaseⅠ degradation during KD acute phase are associated with the patient’s condition , and dynamic monitoring of cfDNA has certain clinical value in early diagnosis and assessment of condition severity. NETs may be involved in the vascular inflammatory endothelial injury and coagulation axis reaction of KD. Furthermore, it suggests that IVIG exerts the pharmacological protective effect by reducing the damage of NETs pathway

参考文献/References:

[1].Rife E,Gedalia A. Kawasaki disease:an update[J]. Curr Rheumatol Rep,2020,22(10):75.
[2].Soni PR,Noval Rivas M,Arditi M. A comprehensive update on Kawasaki disease vasculitis and myocarditis[J]. Curr Rheumatol Rep,2020,22(2):6.
[3].中国医师协会儿科医师分会风湿免疫学组,樊志丹,俞海国,等. 中国儿童血管炎诊断与治疗系列专家共识之四——川崎病[J]. 中国实用儿科杂志,2023,38(7):481-488.
[4].黄国英. 川崎病流行病学研究进展和思考[J]. 中国小儿急救医学,2020,27(9):641-644.
[5].范雪,徐明国. 川崎病发病机制及治疗研究进展[J]. 中国实用儿科杂志,2021,36(5):339-344.
[6].蒋瑶,邢艳.中性粒细胞胞外诱捕网形成的分子机制研究进展[J]. 中国免疫学杂志,2022,38(10):1272-1277.
[7].Papayannopoulos V. Neutrophil extracellular traps in immunity and disease[J]. Nat Rev Immunol,2018,18(2):134-147.
[8].程怡,陈亚琳,相新新.中性粒细胞胞外诱捕网在相关疾病中的作用[J].生命的化学,2023,43(5):735-741.
[9].Denning NL,Aziz M,Gurien SD,et al. DAMPs and NETs in sepsis[J]. Front Immunol, 2019,10:2536.
[10].王瀚黎,田圆,梁群. 中性粒细胞胞外诱捕网在脓毒症中的作用机制与靶点[J]. 疑难病杂志,2022,21(11):1206-1210.
[11].Ebrahimi F,Giaglis S,Hahn S,et al. Markers of neutrophil extracellular traps predict adverse outcome in community-acquired pneumonia:secondary analysis of a randomised controlled trial[J]. Eur Respir J,2018,51(4):1701389.
[12].俞灵盈.中性粒细胞胞外捕获网介导川崎病血管损伤的机制研究[D]. 贵州:遵义医科大学,2022.
[13].蔡泽波,韦明,贾高泉,等. 小儿川崎病EMPs、TNF-α、IL-6的水平变化及其与冠状动脉病变的关系[J]. 吉林医学,2022,43(4):922-925.
[14].Xu J,Zhang X,Pelayo R,et al. Extracellular histones are major mediators of death in sepsis[J]. Nat Med,2009,15(11):1318-1321.
[15].Blanco LP,Wang X,Carlucci PM,et al. RNA externalized by neutrophil extracellular traps promotes inflammatory pathways in endothelial cells[J]. Arthritis Rheumatol,2021,73(12):2282-2292.
[16].胡琳,杨艳娟,李洁滢,等. 红景天苷通过激活PI3K/Akt和抑制NF-κB信号通路改善川崎病冠状动脉损伤[J].实用医学杂志,2022,38(21):2657-2662,2669.
[17].Novotny J,Chandraratne S,Weinberger T,et al. Histological comparison of arterial thrombi in mice and men and the influence of Cl-amidine on thrombus formation[J]. PLoS One,2018,13(1):e0190728.
[18].陈丹,杨晓林,沈照波,等. 中性粒细胞胞外网状陷阱及相关标志物对儿童社区获得性肺炎诊断的价值[J]. 中国当代儿科杂志,2019,21(9):868-875.
[19].Fisher J,Mohanty T,Karlsson CAQ,et al. Proteome profiling of recombinant DNase therapy in reducing NETs and aiding recovery in COVID-19 patienst[J]. Mol Cell Proteomics,2021,20:100113.
[20].陕西省川崎病诊疗中心,陕西省儿童内科疾病临床医学研究中心,陕西省人民医院儿童病院,等. 静脉输注免疫球蛋白在儿童川崎病中应用的专家共识[J]. 中国当代儿科杂志,2021,23(9):867-876.
[21].高立超,龚方戚. 血小板-白细胞聚集体及其在川崎病发病中的研究进展[J]. 中国当代儿科杂志,2023(6):587-594.
[22].王瑞青,郑彩虹,朱巍,等.血小板微粒介导miR-4306调控糖尿病大鼠主动脉血管内皮细胞损伤的作用及机制研究[J].中国比较医学杂志,2021(9):105-112.
[23].Jakob A,Schachinger E,Klau S,et al. Von willebrand factor parameters as potential biomarkers for disease activity and coronary artery lesion in patients with Kawasaki disease[J]. Eur J Pediatr, 2020,179(3):377-384.
[24].蔡泽波,于力,韦明,等. 循环内皮细胞、内皮细胞微粒检测对不完全川崎病的辅助诊断价值[J]. 广东医学,2020,(16):1655-1658.
[25].Jin J,Wang J,Lu Y,et al. Platelet-derived microparticles:a new index of monitoring platelet activation and inflammation in Kawasaki disease[J]. Indian J Pediatr,2019,86(3):250-255.

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更新日期/Last Update: 2024-12-02