重型血友病A患儿关节出血后IL-1β、IL-6、TNF-α释放与关节病变形成的相关性研究

doi:10.3969/j.issn.1006-7795.2018.03.002

首都医科大学学报 ›› 2018, Vol. 39 ›› Issue (3): 314-319.doi: 10.3969/j.issn.1006-7795.2018.03.002

• 血液病学基础与临床研究 • 上一篇下一篇

重型血友病A患儿关节出血后IL-1β、IL-6、TNF-α释放与关节病变形成的相关性研究

刘国青, 陈振萍, 唐凌, 吴心怡, 甄英姿, 李刚, 王岩, 张宁宁, 张纪水, 于国霞, 吴润晖

首都医科大学附属北京儿童医院血液肿瘤中心儿童血液病与肿瘤分子分型北京市重点实验室儿科学国家重点学科教育部儿童重大疾病重点实验室, 北京 100045

收稿日期:2018-03-08 出版日期:2018-05-21 发布日期:2018-06-11
通讯作者: 吴润晖 E-mail:runhuiwu@hotmail.com
基金资助:
北京市自然科学基金（7162059），首都卫生发展科研专项（首发-2014-2-2092），北京市医院管理局临床医学发展专项（ZY201404），诺和诺德基金项目。

Release of cytokines after joint bleeding and the formation of haemophilic arthropathy in children with severe hemophilia A

Liu Guoqing, Chen Zhenping, Tang Ling, Wu Xinyi, Zhen Yingzi, Li Gang, Wang Yan, Zhang Ningning, Zhang Jishui, Yu Guoxia, Wu Runhui

Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University;Beijing Key Laboratory of Pediatric Hematology Oncology;MOE Key Laboratory of Major Diseases in Children, National Key Discipline of Pediatrics, Ministry of Education, Beijing 100045, China

Received:2018-03-08 Online:2018-05-21 Published:2018-06-11
Supported by:
This study was supported by Natural Science Foundation of Beijing (7162059), Capital Health Research and Development of Special (2014-2-2092),Beijing Municipal Administration of Hospital Clinical Medicine Development(ZY201404), the NOVO Nordisk Funding Project.

摘要/Abstract

摘要： 目的探索重型血友病A患儿关节出血后炎性反应因子白细胞介素-1β（interleukin-1β，IL-1β）、白细胞介素-6（interleukin-6，IL-6）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）在形成关节病变中的作用，为进一步开展血友病关节病变防控提供理论依据。方法收集2015年10月至2016年4月于首都医科大学附属北京儿童医院血友病门诊就诊、符合入组条件的血友病A患儿，记录患儿关节出血情况，根据患儿关节出血情况进行分组：无关节出血（non-joint bleeding，NJB）组和关节出血（joint bleeding，JB）组，后者包括急性关节出血（acute joint bleeding，AJB）组与慢性关节出血（chronic joint bleeding，CJB）组，留取外周静脉血标本，用酶联免疫吸附实验（enzyme-linked immunosorbent assay，ELISA）检测血清中IL-1β、IL-6及TNF-α的表达水平，用反转录-聚合酶链反应（reverse transcription-polymerase chain reaction，RT-PCR）检测细胞内IL-1β、IL-6、TNF-α的mRNA表达水平，收集实验数据并进行统计学分析。结果共入组患儿47例，其中无关节出血组17例、急性关节出血组17例（有关节病变者8例，无关节病变者9例）、慢性关节出血组13例，入组患儿中位年龄5.5（2~18）岁。急性关节出血组、慢性关节出血组与无关节出血组的TNF-α的细胞内mRNA的水平差异有统计学意义（P<0.05），且急性关节出血组、慢性关节出血组的TNF-α的细胞内mRNA的水平均高于无关节出血组（P<0.05）。急性关节出血组伴关节病变与急性关节出血组不伴关节病变的TNF-α的细胞内mRNA的水平（5.584±3.634 vs 1.680±1.590）差异有统计学意义（P=0.02）。结论重型血友病A患儿关节出血急性期IL-1β、IL-6、TNF-α表达升高，以TNF-α升高为主，慢性期只见TNF-α表达升高，伴有关节病变的患儿TNF-α表达水平明显升高，故TNF-α是关节病变形成的关键因子。

关键词: 重型血友病A, 关节病变, 炎性因子

Abstract: Objective To explore the role of inflammatory factors[interleukin-1β(IL-1β),interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α)] in the formation of haemophilic arthropathy in children with severe hemophilia A, and to provide theoretical basis for further prevention and treatment target of hemophilia joint disease.Methods The eligibility hemophilia A children were enrolled from the Hemophilia Outpatient Clinic of Beijing Children Hospital during 2015-2016. Patients were divided into non-joint bleeding(NJB) group, joint bleeding(JB) group[acute joint bleeding(AJB) group, chronic joint bleeding(CJB) group]. Peripheral venous blood was collected, the expression of IL-1β, IL-6 and TNF-α in blood serum were detected by enzyme-linked immunosorbent assay (enzyme-linked immunosorbent assay, ELISA). The expression of mRNA of IL-1β, IL-6 and TNF-α was detected by reverse transcription-polymerase chain reaction (RT-PCR).Statistical analysis the levels of IL-1β, IL-6 and TNF-α in blood serum and their mRNA expression.Results A total of 47 cases were collected in the patients group, including 17cases of NJB group, 17 cases of AJB group (8 cases with target joint, 9 cases without target joint) and 13 cases of CJB group. Median age was 5.5 years (2 years to18 years). There was significant difference in the expression of mRNA of TNF-α between NJB group, JB group and AJB group(P<0.05). There was significant difference in the expression of mRNA of TNF-α between AJB group with arthropathy (n=8, 5.584±3.634) and AJB group without arthropathy (n=9, 1.680±1.590) (P=0.02).Conclusion The expression of IL-1β, IL-6 and TNF-α in children with hemophilia increased in acute joint bleeding, and the expression of TNF-α increased mainly in acute, chronic and with haemophilic arthropathy, so TNF-α is the key of cytokines in the formation of haemophilic arthropathy in children with severe hemophilia A.

Key words: children with severe hemophilia A, haemophilic arthropathy, inflammatory factors

中图分类号:

R554⁺.1

刘国青, 陈振萍, 唐凌, 吴心怡, 甄英姿, 李刚, 王岩, 张宁宁, 张纪水, 于国霞, 吴润晖. 重型血友病A患儿关节出血后IL-1β、IL-6、TNF-α释放与关节病变形成的相关性研究[J]. 首都医科大学学报, 2018, 39(3): 314-319.

Liu Guoqing, Chen Zhenping, Tang Ling, Wu Xinyi, Zhen Yingzi, Li Gang, Wang Yan, Zhang Ningning, Zhang Jishui, Yu Guoxia, Wu Runhui. Release of cytokines after joint bleeding and the formation of haemophilic arthropathy in children with severe hemophilia A[J]. Journal of Capital Medical University, 2018, 39(3): 314-319.

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重型血友病A患儿关节出血后IL-1β、IL-6、TNF-α释放与关节病变形成的相关性研究

Release of cytokines after joint bleeding and the formation of haemophilic arthropathy in children with severe hemophilia A

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