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目的探讨在支气管哮喘中神经生长因子(NGF)对T1亚群辅助淋巴细胞(Th1)与T2亚群辅助淋巴细胞(Th2)类细胞因子表达的调控作用机制。方法于2004年3月至2004年12月对中南大学湘雅二医院应用鸡卵清蛋白(OVA)建立鼠哮喘模型,并将SD大鼠随机分为4组:哮喘组、正常对照组、外源性NGF干预组(NGF组)、抗NGF抗体干预组(抗NGF抗体组),每组8只。模型建立后取肺组织分别作以下研究:通过逆转录-聚合酶链反应(RT-PCR)半定量检测哮喘组和对照组NGFmRNA;同时测定4组Th1类细胞因子干扰素-γ(IFN-γ)、Th2类细胞因子白细胞介素4(IL-4)的mRNA表达改变。结果(1)哮喘组与对照组相比较:肺组织NGFmRNA表达明显增强[(90.4±7.6)%对(51.8±12.3)%,P<0.01];IL-4mRNA表达明显增强[(48.0±8.1)%对(19.4±8.4)%,P<0.05],IFN-γmRNA表达明显减低[(32.8±8.1)%对(43.4±8.9)%,P<0.01];哮喘组中肺组织的NGFmRNA相对表达量与IFN-γ/IL-4mRNA表达比值呈显著负相关(r=-0.963,P<0.01)。(2)NGF组与哮喘组相比较,IL-4mRNA表达显著增高[(62.0±12.2)%对(48.0±8.1)%,P<0.01];IFN-γmRNA表达显著降低[(19.9±8.1)%对(32.8±8.1)%,P<0.01]。(3)抗NGF抗体干预组与哮喘组相比较,肺组织中IL-4mRNA表达显著减低[(20.1±7.1)%对(48.0±8.1)%,P<0.01],IFN-γmRNA表达显著增高[(45.4±9.4)%对(32.8±8.1)%,P<0.05]。结论NGF下调Th1类细胞因子表达,上调Th2类细胞因子表达,由此参与促进放大哮喘Th1/Th2类细胞因子免疫失衡效应。
Objective To investigate the regulatory mechanism of nerve growth factor (NGF) on the expression of Th1 and T2 subtypes of Th2 cytokines in T1 asthma bronchial asthma. Methods From March 2004 to December 2004, a rat model of asthma was established by applying chicken ovalbumin (OVA) to the Second Xiangya Hospital of Central South University. SD rats were randomly divided into four groups: asthma group, normal control group, NGF intervention group (NGF group), anti-NGF antibody intervention group (anti-NGF antibody group), 8 in each group. Lung tissue samples were taken for the following studies: NGF mRNA was detected semiquantitatively by reverse transcription-polymerase chain reaction (RT-PCR) in the asthmatic and control groups; IFN-γ ), Th2 cytokine interleukin-4 (IL-4) mRNA expression changes. Results (1) Compared with the control group, the expression of NGF mRNA in lung tissue was significantly increased in asthmatic group [(90.4 ± 7.6)% vs (51.8 ± 12.3)%, P <0.01] (32.8 ± 8.1)% versus (43.4 ± 8.9)%, P <0.01]. The relative expression of NGF mRNA in lung tissue of asthmatic group was significantly higher than that in control group (19.4 ± 8.4% vs P <0.05) Negatively correlated with the ratio of IFN-γ / IL-4 mRNA expression (r = -0.963, P <0.01). (2) The expression of IL-4 mRNA in NGF group was significantly higher than that in asthma group [(62.0 ± 12.2)% vs (48.0 ± 8.1)%, P <0.01] For (32.8 ± 8.1)%, P <0.01]. (3) Compared with the asthma group, the expression of IL-4mRNA in lung tissue was significantly decreased in the anti-NGF antibody-treated group (20.1 ± 7.1% vs 48.0 ± 8.1%, P <0.01) (45.4 ± 9.4)% versus (32.8 ± 8.1)%, P <0.05]. Conclusion NGF down-regulates the expression of Th1 cytokines and up-regulates the expression of Th2 cytokines, which is involved in the promotion of immune imbalance of Th1 / Th2 cytokines in asthmatic rats.