目的：检测咳嗽变异性哮喘（CVA）患儿诱导痰中神经生长因子（NGF）和白细胞介素-4（IL-4）的表达，探讨NGF和IL-4在小儿CVA中的作用。方法：34例CVA患儿纳入研究，20例健康儿童作为正常对照。对受试者进行痰诱导，苏木精-伊红染色计数诱导痰中嗜酸性粒细胞的百分比。酶联免疫吸附双抗体夹心法检测诱导痰液上清中NGF和IL-4的表达。荧光定量PCR检测诱导痰液沉淀细胞中NGF和IL-4 mRNA的表达。结果：CVA组患儿诱导痰中嗜酸性粒细胞百分数为（13.4±3.6）%，显著高于对照组的（2.6±1.7）%（P<0.01）。CVA组患儿诱导痰上清中NGF和IL-4的表达水平及诱导痰沉淀细胞中NGF和IL-4 mRNA的表达水平均显著高于对照组，差异有统计学意义（均P<0.05）。诱导痰上清中NGF和IL-4的表达水平及诱导痰中NGF和IL-4 mRNA的表达水平与嗜酸性粒细胞计数均呈正相关（均P<0.05）。CVA患儿治疗后诱导痰上清中NGF和IL-4的表达水平及诱导痰中NGF和IL-4 mRNA的表达水平均出现了显著的减低（均P<0.05）。结论：嗜酸性粒细胞的浸润和炎性介质NGF、IL-4的升高参与了小儿CVA的发生发展过程，在小儿CVA的诊断和治疗中具有一定的价值。
Abstract
OBJECTIVE: To examine the levels of nerve growth factor (NGF) and interleukin-4 (IL-4) in the induced sputum of children with cough variant asthma (CVA), with the aim of studying the roles of NGF and IL-4 in childhood CVA. METHODS: Thirty-four children with CVA were enrolled in this study. Twenty healthy children were used as a normal control group. The induced sputum was separated into supernatant and cells. Hematoxylin and eosin staining was used to count differential cells. The expression of NGF and IL-4 in supernatant was measured using ELISA. The mRNA expression of NGF and IL-4 in cells was determined by Real-time PCR analysis. RESULTS: The percentage of eosinophils in the CVA group was significantly higher than in the control group [(13.4±3.6)% vs (2.6±1.7)%; P<0.01]. The expression of NGF and IL-4 protein and mRNA in induced sputum was significantly higher in the CVA group than in the control group (P<0.05). The expression of NGF and IL-4 protein and mRNA was positively correlated with the percentage of eosinophils (P<0.01). The expression of NGF and IL-4 protein and mRNA in induced sputum was significantly reduced in the CVA group after treatment (P<0.05). CONCLUSIONS: Eosinophils infiltration and increased expression of NGF and IL-4 play key roles in the development of childhood CVA, suggesting that they may be useful in the diagnosis and treatment of childhood CVA.
关键词
咳嗽变异性哮喘 /
神经生长因子 /
白细胞介素-4 /
儿童
Key words
Cough variant asthma /
Nerve growth factor /
Interleukin-4 /
Child
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
［1］苗青, 魏鹏草. 咳嗽变异性哮喘的研究进展［J］. 实用医学杂志, 2011, 27(10):1717-1718.
［2］Takemura M, Niimi A, Matsumoto H, Ueda T, Yamaguchi M, Matsuoka H, et al. Atopic features of cough variant asthma and classic asthma with wheezing［J］. Clin Exp Allergy, 2007, 37(12): 1833-1839.
［3］Matsumoto H, Niimi A, Tabuena RP, Takemura M, Ueda T, Yamaguchi M, et al. Airway wall thickening in patients with cough variant asthma and nonasthmatic chronic cough［J］. Chest, 2007, 13l(4): 1042-1049.
［4］Curtis JL. Cell-mediated adaptive immune defense of the lungs［J］. Proc Am Thorac Soc, 2005, 2(2): 412-416
［5］中华医学会儿科学分会呼吸学组, 中华医学会《中华儿科杂志》编辑委员会.儿童支气管哮喘防治常规［J］.中华儿科杂志, 2004, 42(2): 100-104.
［6］彭秋凤, 孔灵菲. 咳嗽变异性哮喘患者诱导痰中神经生长因子和白细胞介素-4水平及气道炎症特征初探［J］. 中华内科杂志, 2011, 50(3): 221-224.
［7］张晓燕, 刘春风, 焦富勇. 小儿慢性咳嗽的诊断探讨［J］. 中国儿童保健杂志, 2005, 13(1): 47-49.
［8］Matsumoto H, Niimi A, Takemura M, Ueda T, Yamaguchi M, Matsuoka H, et al. Features of cough variant asthma and classic asthma during methacholine-induced brochoconstriction: a cross-sectional study［J］. Cough, 2009, 5: 3.
［9］Freund-Michel V, Bertrand C, Frossard N. TrkA signalling pathways in human airway smooth muscle cell proliferation［J］. Cell Signal, 2006, 18(5): 621-627.
［10］El-Hashim AZ, Jaffal SM. Nerve growth factor enhances cough and airway obstruction via TrkA receptor-and TRPVl-dependent mechanisms［J］. Thorax, 2009, 64(9): 79l-797.
［11］Meng L, He X, Zhu W, Yang X, Jiang C, Sun Q, et al. TLR3 and TLR7 modulate IgE production in antigen induced pulmonary inflammation via influencing IL-4 expression in immune organs［J］. PLoS One, 2011, 6(2): e17252.
［12］Nassenstein C, Braun A, Erpenbeck VJ, Lommatzsch M, Schmidt S, Krug N, et al. The neurotrophins nerve growth factor, brain-derived neurotrphic factor, neurotrophin-3, and neurotrophin-4 are survival and activation factors for eosinophils in patients with allergic bronchial asthma［J］. J Exp Med, 2003, 198(3): 455-467.
PDF(1061 KB)
