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抗神经生长因子抗体通过下调RhoA改善气道高反应性。

Anti-nerve growth factor antibody improves airway hyperresponsiveness by down-regulating RhoA.

作者信息

Chen Jingying, Kou Lijie, Kong Lingfei

机构信息

a Institute of Respiratory Diseases, The First Hospital of China Medical University , Shenyang , China.

b Department of ICU , Peking University Shenzhen Hospital , Shenzhen , China.

出版信息

J Asthma. 2018 Oct;55(10):1079-1085. doi: 10.1080/02770903.2017.1396467. Epub 2018 Apr 3.

DOI:10.1080/02770903.2017.1396467
PMID:29611766
Abstract

BACKGROUND

The pathogenesis of asthma is complex and continues to be considered as a challenging subject. Some studies have shown that nerve growth factor (NGF) participates in the pathogenesis of asthma, but the mechanism of airway contraction caused by NGF is still unclear.

OBJECTIVE

Our aim was to discuss the effect of anti-NGF antibody on RhoA expression, and further explore the role of NGF in airway hyperresponsiveness (AHR).

METHODS

Thirty female BALB/c mice were divided into three groups randomly: control group (group C, n = 10), asthma group (group A, n = 10) and anti-NGF antibody intervention group (group N, n = 10). The asthmatic mice were stimulated by OVA suspension, the intervention mice were given nasal instillation of anti-NGF antibody before the stimulation. Airway responsiveness, eosinophils, IL-13, IFN-γ were measured. The protein expression and mRNA level of NGF and RhoA were detected by immunohistochemical and Real Time-PCR (RT-PCR) analyses.

RESULTS

Airway responsiveness, eosinophils and IL-13 levels in group A were significantly increased compare with the other groups, and significantly decreased in group N than those in group A. IFN-γ level was significantly reduced in group A and increased in group N. Immunohistochemistry and RT-PCR analyses showed that the protein expression and mRNA level of NGF and RhoA were significantly increased in group A and significantly decreased in group N.

CONCLUSION

NGF participates in the pathogenesis of asthma in mice. Anti-NGF antibody can inhibit airway inflammation and alleviate AHR by down-regulating the protein expression and mRNA level of RhoA.

摘要

背景

哮喘的发病机制复杂,一直是一个具有挑战性的研究课题。一些研究表明神经生长因子(NGF)参与哮喘的发病机制,但NGF引起气道收缩的机制仍不清楚。

目的

探讨抗NGF抗体对RhoA表达的影响,进一步探究NGF在气道高反应性(AHR)中的作用。

方法

将30只雌性BALB/c小鼠随机分为三组:对照组(C组,n = 10)、哮喘组(A组,n = 10)和抗NGF抗体干预组(N组,n = 10)。用OVA悬液刺激哮喘小鼠,干预组小鼠在刺激前经鼻滴注抗NGF抗体。检测气道反应性、嗜酸性粒细胞、IL-13、IFN-γ。通过免疫组织化学和实时荧光定量PCR(RT-PCR)分析检测NGF和RhoA的蛋白表达及mRNA水平。

结果

与其他组相比,A组气道反应性、嗜酸性粒细胞和IL-13水平显著升高,N组比A组显著降低。A组IFN-γ水平显著降低,N组升高。免疫组织化学和RT-PCR分析显示,A组NGF和RhoA的蛋白表达及mRNA水平显著升高,N组显著降低。

结论

NGF参与小鼠哮喘的发病机制。抗NGF抗体可通过下调RhoA蛋白表达及mRNA水平抑制气道炎症并减轻AHR。

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