幼年特发性关节炎患儿Notch信号通路相关基因表达的意义  

Expressions and significance of Notch signal pathway and target gene in children with juvenile idiopathic arthritis

作　　者：陈挚[1] 程苏云 李洪伟[1] 谢颖[1] 李丰[1] 曾萍[1] 孙广超 陈香元 曾华松[1] Chen Zhi;Cheng Suyun;Li Hongwei;Xie Ying;Li Feng;Zeng Ping;Sun Guangchao;Chen Xiangyuan;Zeng Huasong(Department of Pediatric Allergy, Immunology and Rheumatology, Guangzhou Women and Children＇s Medical Center of Guangzhou Medical University, Guangzhou 510000, China Now Working in Department of Pediatrics, Hunan Children＇s Hospital)

机构地区：[1]广州医科大学附属广州市妇女儿童医疗中心过敏免疫风湿病科,510000

出　　处：《中华实用儿科临床杂志》2017年第21期1628-1631,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：广东省科技厅项目（2014A020212010）;广州市科技计划项目（2016070103）

摘　　要：目的分析幼年特发性关节炎（JIA）患儿Notch信号通路与淋巴细胞及细胞因子水平的关系，探讨其在JIA发病机制中的作用。方法选择2015年11月至2016年2月在广州市妇女儿童医疗中心过敏免疫风湿科诊断的35例JIA患儿（JIA组），男20例，女15例；年龄（6．5±4．0）岁（0．83～15．00岁）。其中全身型组22例，关节型组13例（多关节型7例，少关节型6例）。健康对照组15例，男6例，女9例；年龄（5．0±2．9）岁（1．0～11．0岁）。采用实时荧光定量PCR检测JIA组和健康对照组外周血中Notch受体、配体及靶基因mR-NA的表达水平；ELISA法测定2组血浆中白细胞介素（IL）-1p、IL-10、IL-6、IL-17、转化生长因子-（TGF-B）及IL_4细胞因子水平。结果与健康对照组比较，JIA组外周血中Notch2（0．4±0．3比1．6±3．2）、Jaggedl（11．3±1．2比44．0±79．0）及HES1（0．1±0．1比0．4±0．3）mRNA均高表达，差异均有统计学意义（均P〈0．05）。JIA组与健康对照组比较，血浆中IL-1B水平升高[（182．22±309．13）ng／L比（54．71±20．33）ng／L]，IL-10水平升高[（32．99±34．28）ng／L比（22．68±4．56）ng／L]，IL-6水平升高[（100．48±305．57）ng／L比（13．98±2．78）ng／L]，IL-17水平升高[（9．11±17．57）ng／L比（2．42±0．29）ng／L]，TGF—B水平升高[（14．37±9．33）ng／L比（5．49±4．49）ng／L]，差异均有统计学意义（均P〈0．05）。全身型JIA患儿外周血中HESlmRNA表达量与STAT3mRNA表达量呈正相关（r=0．573，P〈0．05）；全身型组JIA患儿外周血中HESlmRNA水平与CD3^＋T淋巴细胞（r=0．528）、CD19^＋B淋巴细胞（r=0．480）、CD3^＋CD8^＋抑制T淋巴细胞（r=0．457）、CD16^＋CD56^＋NK细胞（r=0．598）数量呈正相关（均P〈0．05）；关节型组JIA患儿外周血中HESlmRNA水平与CD3^＋T淋巴细胞数量呈正相关（r=0．577，P〈0．05）。结论Notch�Objective To analyze the relationship between Notch signaling pathway and levels of lymphoeytes and eytokines in children with juvenile idiopathic arthritis （JIA） , and to explore its role in the pathogenesis of JIA. Methods Thirty - five pediatric patients with JIA [ males 20 cases, females 15 cases ; aged （ 6.5 ± 4.0 ） years old, （0.83 - 15.00 years old） ] and 15 healthy children [ males 6 cases, females 9 cases ; aged （ 5.0 ± 2.9 ） years old, （1.0- 11.0 years old）] from November 2015 to February 2016 in Guangzhou Women and Children＇s Medical Center were included in the study. The JIA group were divided into the systemonset JIA（ So -JIA） group （22 cases） and pso- riatic JIA（ p -JIA） group （13 cases, polyarthritis 7 cases and oligoarthritis 6 cases）. The expressions of Notch signa- ling＇s receptor, ligand and target gene mRNA in peripheral blood monouclear cells （PBMC） from the JIA group and the control group were determined by quantitative real - time PCR. The levels of cytokines interleukin （IL） - 1 [3, IL- 10, IL- 6, IL- 17, IL- 4 and transforming growth factor- β （TGF- β） were detected by enzyme -linked im- munosorbent assay. Results Compared with the healthy control group, the Notch2 receptors （ 1.6 ± 3.2 vs. 0. 4 ± 0.3） expression level, Jaggedl ligand （44.0 ± 79.0 vs. 11.3 ± 1.2） expression levels and the levels of target gene HES1 （0.4 ± 0. 3 vs. 0.1 ± 0.1 ） mRNA in the JIA group showed a significant increase, and the differences were all statistically significant （all P 〈 0.05 ）. Compared with the healthy control group, the JIA group showed an increased level oflL-113 [（182.22 ±309.13） ng/Lvs. （54.71±20.33） ng/L], IL-10 [（32.99±4.28） ng/L vs. （22.68±4.56） ng/Ll, IL-6 [（100.48±305.57） ng/Lvs. （13.98±2.78） ng/L], IL-17 [（9.11±17.57） ng/L vs. （2.42 ±0.29） ng/L] and TGF - [3 [ （14.37 ±9.33） ng/L vs. （5.49 ±4.49） ng/L ,and there were statistically significant differences （ all P

关 键 词：幼年特发性关节炎 NOTCH信号通路 淋巴细胞 细胞因子 

分 类 号：R725.9[医药卫生—儿科]