川崎病患儿血浆中可溶性内皮细胞蛋白C受体、一氧化氮的表达及与炎症反应和冠状动脉病变的关系
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摘要
目的:研究川崎病患儿血浆中可溶性内皮细胞蛋白C受体(s EPCR)、一氧化氮(NO)的表达及与炎症反应和冠状动脉病变(CAL)的关系。方法:选择2016年12月至2018年2月盘锦市中心医院收治的川崎病患儿104例为川崎病组,根据患儿彩色超声心动图检测结果将川崎病组分为CAL组30例和非CAL组(NCAL组)74例。另选取同期于我院进行体检的健康儿童56例为对照组。比较川崎病组与对照组、川崎病组患儿急性期与缓解期、CAL组与NCAL组s EPCR、NO、C-反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平,并分析川崎病患儿s EPCR、NO与炎症因子及CAL的相关性。结果:川崎病组患儿s EPCR、NO、CRP、IL-6、TNF-α水平均高于对照组,差异有统计学意义(P<0.05)。川崎病组患儿急性期s EPCR、NO、CRP、IL-6、TNF-α水平均高于缓解期,差异有统计学意义(P<0.05)。CAL组s EPCR、NO、CRP、IL-6、TNF-α水平均高于NCAL组,差异有统计学意义(P<0.05)。经Pearson相关性分析结果显示,川崎病患儿s EPCR、NO与CRP、IL-6、TNF-α及CAL均呈正相关(P<0.05)。结论:川崎病患儿s EPCR、NO水平与炎性因子及CAL相关,s EPCR、NO可能在其炎症反应及CAL进展中起到一定的作用。
Objective: To study the expression of plasma soluble endothelial protein C receptor(s EPCR) and nitric oxide(NO) in children with Kawasaki disease and its relationship with inflammatory reaction and coronary artery disease(CAL). Methods: 104 children with Kawasaki disease who were treated in Central Hospital of Panjin from December 2016 to February 2018 were selected as Kawasaki disease group, according to the results of color echocardiography, the children of Kawasaki disease group were divided into CAL group with 30 cases and non CAL group(NCAL group) with 74 cases. In addition, 56 healthy children who were received healthy physical examination in our hospital at the same time were selected as the control group. The levels of s EPCR, NO, C-reactive protein(CRP), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were compared between the Kawasaki disease group and the control group, the acute stage and remission stage of children in the Kawasaki disease group, the CAL group and the NCAL group. The correlation of s EPCR, NO and inflammatory factors, CAL of Kawasaki disease were analyzed. Results: The levels of s EPCR, NO, CRP, IL-6, TNF-α of Kawasaki disease group were higher than the control group,the difference was statistically significant(P<0.05).The levels of s EPCR, NO, CRP,TNF-α, IL-6 in acute stage of Kawasaki disease group were higher than those in remission stage, the difference was statistically significant(P<0.05). The levels of s EPCR, NO, CRP, TNF-α and IL-6 in CAL group were higher than those in NCAL group, and the difference was statistically significant(P<0.05). The results of Pearson correlation analysis showed that s EPCR and NO were positively correlated with CRP, IL-6, TNF-α and CAL in children with Kawasaki disease(P<0.05). Conclusion: The levels of s EPCR and NO in children with Kawasaki disease are related to inflammatory factors and CAL, s EPCR and NO may play a certain role in its inflammatory response and CAL progression.
Objective: To study the expression of plasma soluble endothelial protein C receptor(s EPCR) and nitric oxide(NO) in children with Kawasaki disease and its relationship with inflammatory reaction and coronary artery disease(CAL). Methods: 104 children with Kawasaki disease who were treated in Central Hospital of Panjin from December 2016 to February 2018 were selected as Kawasaki disease group, according to the results of color echocardiography, the children of Kawasaki disease group were divided into CAL group with 30 cases and non CAL group(NCAL group) with 74 cases. In addition, 56 healthy children who were received healthy physical examination in our hospital at the same time were selected as the control group. The levels of s EPCR, NO, C-reactive protein(CRP), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were compared between the Kawasaki disease group and the control group, the acute stage and remission stage of children in the Kawasaki disease group, the CAL group and the NCAL group. The correlation of s EPCR, NO and inflammatory factors, CAL of Kawasaki disease were analyzed. Results: The levels of s EPCR, NO, CRP, IL-6, TNF-α of Kawasaki disease group were higher than the control group,the difference was statistically significant(P<0.05).The levels of s EPCR, NO, CRP,TNF-α, IL-6 in acute stage of Kawasaki disease group were higher than those in remission stage, the difference was statistically significant(P<0.05). The levels of s EPCR, NO, CRP, TNF-α and IL-6 in CAL group were higher than those in NCAL group, and the difference was statistically significant(P<0.05). The results of Pearson correlation analysis showed that s EPCR and NO were positively correlated with CRP, IL-6, TNF-α and CAL in children with Kawasaki disease(P<0.05). Conclusion: The levels of s EPCR and NO in children with Kawasaki disease are related to inflammatory factors and CAL, s EPCR and NO may play a certain role in its inflammatory response and CAL progression.
引文
[1]Yokota S,Kikuchi M,Nozawa T,et al.Pathogenesis of systemic inflammatory diseases in childhood:"Lessons from clinical trials of anti-cytokine monoclonal antibodies for Kawasaki disease,systemic onset juvenile idiopathic arthritis,and cryopyrin-associated periodic fever syndrome"[J].Rheumatol Int,2015,35(1):81-84
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[6]Noto N,Komori A,Ayusawa M,et al.Recent updates on echocardiography and ultrasound for Kawasaki disease:beyond the coronary artery[J].Cardiovasc Diagn Ther,2018,8(1):80-89
[7]Wang Z,Weng F,Li C,et al.Neutropenia after intravenous immunoglobulin therapy is associated with coronary artery lesions in children with Kawasaki disease:a case control study[J].BMC Pediatr,2018,18(1):76
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[9]Chiappetta S,Ripa M,Galli L,et al.Soluble endothelial protein C receptor(s EPCR)as an inflammatory biomarker in naive HIV-infected patients during ART[J].J Antimicrob Chemother,2016,71(6):1627-1631
[10]Song R,Liu G,Li X,et al.Elevated Inducible Nitric Oxide Levels and Decreased Hydrogen Sulfide Levels Can Predict the Risk of Coronary Artery Ectasia in Kawasaki Disease[J].Pediatr Cardiol,2016,37(2):322-329
[11]张远达,冀超玉,王静,等.川崎病患儿内源性硫化氢水平改变的意义[J].国际儿科学杂志,2015,42(6):717-719
[12]蒙绪标,符兰芳,刘婷婷,等.可溶性内皮细胞蛋白C受体和高敏C反应蛋白水平预测糖尿病患者血管并发症的价值[J].中国现代医学杂志,2016,26(14):58-62
[13]杨晓东,黄敏.川崎病诊断实验室指标及其临床价值[J].中国实用儿科杂志,2013,28(7):491-494
[14]汪燕,鲁利群,宁雪梅,等.川崎病患儿的心率变异性指标与血清NT-pro BNP及c TnI水平的相关性[J].现代生物医学进展,2016,16(22):4295-4297
[15]Nakamura Y,Yashiro M,Yamashita M,et al.Cumulative incidence of Kawasaki disease in Japan[J].Pediatr Int,2018,60(1):19-22
[16]Qureshi AM,Agrawal H.Catheter-based anatomic and functional assessment of coronary arteries in anomalous aortic origin of a coronary artery,myocardial bridges and Kawasaki disease[J].Congenit Heart Dis,2017,12(5):615-618
[17]Kaneko U,Kashima Y,Hashimoto M,et al.Very Late Stent Migration Within a Giant Coronary Aneurysm in a Patient With Kawasaki Disease:Assessment With Multidetector Computed Tomography[J].JACC Cardiovasc Interv,2017,10(17):1799-1800
[18]Ishikawa T,Seki K.The association between oxidative stress and endothelial dysfunction in early childhood patients with Kawasaki disease[J].BMC Cardiovasc Disord,2018,18(1):30
[19]Choi JE,Kang HW,Hong YM,et al.C-reactive protein and N-terminal pro-brain natriuretic peptide discrepancy:a differentiation of adenoviral pharyngoconjunctival fever from Kawasaki disease[J].Korean J Pediatr,2018,61(1):12-16
[20]Chen YC,Shen CT,Wang NK,et al.High Sensitivity C Reactive Protein(hs-CRP)in Adolescent and Young Adult Patients with History of Kawasaki Disease[J].Acta Cardiol Sin,2015,31(6):473-477
[21]Sato S,Kawashima H,Kashiwagi Y,et al.Inflammatory cytokines as predictors of resistance to intravenous immunoglobulin therapy in Kawasaki disease patients[J].Int J Rheum Dis,2013,16(2):168-172
[22]Matsui M,Okuma Y,Yamanaka J,et al.Kawasaki disease refractory to standard treatments that responds to a combination of pulsed methylprednisolone and plasma exchange:Cytokine profiling and literature review[J].Cytokine,2015,74(2):339-342
[23]Okada S,Hasegawa S,Suzuki Y,et al.Acute pericardial effusion representing the TNF-α-mediated severe inflammation but not the coronary artery outcome of Kawasaki disease[J].Scand J Rheumatol,2015,44(3):247-252
[24]Saji T,Takatsuki S,Kobayashi T.Anti TNF-α(infliximab)treatment for intravenous immunoglobulin(IVIG)resistance patients with acute Kawasaki disease the effects of anticytokine therapy[J].Nihon Rinsho,2014,72(9):1641-1649
[25]Zhu Y,Chen Z,Chen X,et al.Serum s EPCR levels are elevated in patients with Alzheimer's disease[J].Am J Alzheimers Dis Other Demen,2015,30(5):517-521
[26]Yilmaz H,Cakmak M,Inan O,et al.Association of ambulatory arterial stiffness index with s EPCR in newly diagnosed hypertensive patients[J].Ren Fail,2015,37(9):1409-1413
[27]Song R,Chou YI,Kong J,et al.Association of endothelial microparticle with NO,e NOS,ET-1,and fractional flow reserve in patients with coronary intermediate lesions[J].Biomarkers,2015,20(6-7):429-435
[28]Yacoub M,Aguib H.Opposing forces and a river into a lake:Relevance to coronary hemodynamics in Kawasaki disease[J].Glob Cardiol Sci Pract,2017,2017(3):e201719
[29]Tasolar H,Eyyüpkoca F,Aktürk E,et al.Endothelial nitric oxide synthase levels and their response to exercise in patients with slow coronary flow[J].Cardiovasc J Afr,2013,24(9-10):355-359
[30]陈彤,范玉平,陈宇翔,等.hs CRP、s EPCR与动静脉内瘘血栓形成的关系[J].标记免疫分析与临床,2015,22(4):294-297
[2]Engelberg R,Martin M,Wrotniak BH,et al.Observational study of Interleukin-21(IL-21)does not distinguish Kawasaki disease from other causes of fever in children[J].Pediatr Rheumatol Online J,2017,15(1):32
[3]Park HR,Han MY,Yoon KL,et al.Mycoplasma Infection as a cause of Persistent Fever after Intravenous Immunoglobulin Treatment of Patients with Kawasaki Disease:Frequency and Clinical Impact[J].Infect Chemother,2017,49(1):38-43
[4]Suganuma E,Niimura F,Matsuda S,et al.Losartan attenuates the coronary perivasculitis through its local and systemic anti-inflammatory properties in a murine model of Kawasaki disease[J].Pediatr Res,2017,81(4):593-600
[5]Huang FC,Kuo HC,Huang YH,et al.Anti-inflammatory effect of resveratrol in human coronary arterial endothelial cells via induction of autophagy:implication for the treatment of Kawasaki disease[J].BMC Pharmacol Toxicol,2017,18(1):3
[6]Noto N,Komori A,Ayusawa M,et al.Recent updates on echocardiography and ultrasound for Kawasaki disease:beyond the coronary artery[J].Cardiovasc Diagn Ther,2018,8(1):80-89
[7]Wang Z,Weng F,Li C,et al.Neutropenia after intravenous immunoglobulin therapy is associated with coronary artery lesions in children with Kawasaki disease:a case control study[J].BMC Pediatr,2018,18(1):76
[8]Takahashi T,Sakakibara H,Morikawa Y,et al.Development of coronary artery lesions in indolent Kawasaki disease following initial spontaneous defervescence:a retrospective cohort study[J].Pediatr Rheumatol Online J,2015,13(1):44
[9]Chiappetta S,Ripa M,Galli L,et al.Soluble endothelial protein C receptor(s EPCR)as an inflammatory biomarker in naive HIV-infected patients during ART[J].J Antimicrob Chemother,2016,71(6):1627-1631
[10]Song R,Liu G,Li X,et al.Elevated Inducible Nitric Oxide Levels and Decreased Hydrogen Sulfide Levels Can Predict the Risk of Coronary Artery Ectasia in Kawasaki Disease[J].Pediatr Cardiol,2016,37(2):322-329
[11]张远达,冀超玉,王静,等.川崎病患儿内源性硫化氢水平改变的意义[J].国际儿科学杂志,2015,42(6):717-719
[12]蒙绪标,符兰芳,刘婷婷,等.可溶性内皮细胞蛋白C受体和高敏C反应蛋白水平预测糖尿病患者血管并发症的价值[J].中国现代医学杂志,2016,26(14):58-62
[13]杨晓东,黄敏.川崎病诊断实验室指标及其临床价值[J].中国实用儿科杂志,2013,28(7):491-494
[14]汪燕,鲁利群,宁雪梅,等.川崎病患儿的心率变异性指标与血清NT-pro BNP及c TnI水平的相关性[J].现代生物医学进展,2016,16(22):4295-4297
[15]Nakamura Y,Yashiro M,Yamashita M,et al.Cumulative incidence of Kawasaki disease in Japan[J].Pediatr Int,2018,60(1):19-22
[16]Qureshi AM,Agrawal H.Catheter-based anatomic and functional assessment of coronary arteries in anomalous aortic origin of a coronary artery,myocardial bridges and Kawasaki disease[J].Congenit Heart Dis,2017,12(5):615-618
[17]Kaneko U,Kashima Y,Hashimoto M,et al.Very Late Stent Migration Within a Giant Coronary Aneurysm in a Patient With Kawasaki Disease:Assessment With Multidetector Computed Tomography[J].JACC Cardiovasc Interv,2017,10(17):1799-1800
[18]Ishikawa T,Seki K.The association between oxidative stress and endothelial dysfunction in early childhood patients with Kawasaki disease[J].BMC Cardiovasc Disord,2018,18(1):30
[19]Choi JE,Kang HW,Hong YM,et al.C-reactive protein and N-terminal pro-brain natriuretic peptide discrepancy:a differentiation of adenoviral pharyngoconjunctival fever from Kawasaki disease[J].Korean J Pediatr,2018,61(1):12-16
[20]Chen YC,Shen CT,Wang NK,et al.High Sensitivity C Reactive Protein(hs-CRP)in Adolescent and Young Adult Patients with History of Kawasaki Disease[J].Acta Cardiol Sin,2015,31(6):473-477
[21]Sato S,Kawashima H,Kashiwagi Y,et al.Inflammatory cytokines as predictors of resistance to intravenous immunoglobulin therapy in Kawasaki disease patients[J].Int J Rheum Dis,2013,16(2):168-172
[22]Matsui M,Okuma Y,Yamanaka J,et al.Kawasaki disease refractory to standard treatments that responds to a combination of pulsed methylprednisolone and plasma exchange:Cytokine profiling and literature review[J].Cytokine,2015,74(2):339-342
[23]Okada S,Hasegawa S,Suzuki Y,et al.Acute pericardial effusion representing the TNF-α-mediated severe inflammation but not the coronary artery outcome of Kawasaki disease[J].Scand J Rheumatol,2015,44(3):247-252
[24]Saji T,Takatsuki S,Kobayashi T.Anti TNF-α(infliximab)treatment for intravenous immunoglobulin(IVIG)resistance patients with acute Kawasaki disease the effects of anticytokine therapy[J].Nihon Rinsho,2014,72(9):1641-1649
[25]Zhu Y,Chen Z,Chen X,et al.Serum s EPCR levels are elevated in patients with Alzheimer's disease[J].Am J Alzheimers Dis Other Demen,2015,30(5):517-521
[26]Yilmaz H,Cakmak M,Inan O,et al.Association of ambulatory arterial stiffness index with s EPCR in newly diagnosed hypertensive patients[J].Ren Fail,2015,37(9):1409-1413
[27]Song R,Chou YI,Kong J,et al.Association of endothelial microparticle with NO,e NOS,ET-1,and fractional flow reserve in patients with coronary intermediate lesions[J].Biomarkers,2015,20(6-7):429-435
[28]Yacoub M,Aguib H.Opposing forces and a river into a lake:Relevance to coronary hemodynamics in Kawasaki disease[J].Glob Cardiol Sci Pract,2017,2017(3):e201719
[29]Tasolar H,Eyyüpkoca F,Aktürk E,et al.Endothelial nitric oxide synthase levels and their response to exercise in patients with slow coronary flow[J].Cardiovasc J Afr,2013,24(9-10):355-359
[30]陈彤,范玉平,陈宇翔,等.hs CRP、s EPCR与动静脉内瘘血栓形成的关系[J].标记免疫分析与临床,2015,22(4):294-297
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