变应性鼻炎小鼠模型鼻黏膜组织重塑和转录因子T-bet/GATA-3的表达

Nasal Mucosa Remodeling and Expression of Transcription Factors T-bet/GATA-3 in Allergic Rhinitis Mouse Model

【目的】建立变应性鼻炎小鼠模型,了解鼻黏膜组织重塑情况,探讨核因子T-bet/GATA-3比值在变应性鼻炎免疫失衡中的意义。【方法】建立卵清蛋白(OVA)诱导的变应性鼻炎小鼠模型;20只BALB/c小鼠随机分为正常组和实验组。HE染色观察呼吸道黏膜炎症变化;ELISA法(酶联免疫吸附法)检测血浆中白细胞介素4(IL-4)和干扰素γ(IFN-γ)的水平;Western blot法检测T-bet、GATA-3蛋白在鼻黏膜组织的表达。【结果】变应性鼻炎小鼠鼻和支气管黏膜均存在组织重塑。与正常组相比,实验组鼻黏膜出现上皮脱落,杯状细胞增生,鳞状上皮组织转化,上皮坏死,固有层和黏膜下层腺体增生,血管扩张,组织水肿,并见特征性的嗜酸性粒细胞浸润。实验组血浆中IL-4和IFN-γ的水平分别是(16.5±4.1)pg/mL和(6.5±1.1)pg/mL,而对照组分别是(7.3±1.7)pg/mL,和(11.4±3.3)pg/mL;实验组血浆中IL-4的含量明显高于对照组,差异具有显著性(P<0.05),而IFN-γ的量低于对照组,差异有统计学意义(P<0.05)。对照组鼻黏膜T-bet/GATA-3蛋白表达量的比值(0.62±0.17),明显高于实验组(0.12±0.03;P<0.05)。【结论】变应性鼻炎小鼠模型鼻黏膜存在组织重塑,可能与转录因子T-bet/GATA-3表达失衡导致下游Th1/Th2细胞免疫失衡和细胞因子IL-4/IFN-γ分泌失调有关。

[ Objective ] To establish an allergic rhinitis mouse model, and understand the condition of nasal mucosa remodeling, and investigate the significance of the nuclear factors T-bet/GATA-3 ratio in the immune disbalance of allergic rhinitis. [ Methods ] The ovalbumin （OVA）-indueed allergic rhinitis mouse model was established. Twenty BALB/e mice were randomly divided into a control group and an experimental group. The changes of the respiratory tract mucosa inflammation were observed by HE staining. The levels of IL-4 and INF-Y in serum were detected by ELISA. The T-bet and GATA-3 protein expression in the nasal mucosa were detected by Western blot analysis. [ Results ] Tissue remodeling existed i＇n both nasal mucosa and bronchial mucosa of the allergic rhinitis mice. Compared to the control group, the nasal mucosa of the experimental group developed epithalaxy, goblet cells hyperplasia, squamous epithelium metaplasia, epithelium necrosis, lamina propria and submucosa gland hyperplasia, vasodilatation, tissue edema, and the characterized eosinophil infiltration. In the experimental group, the levels of IL-4 and INF-3＇ in serum were （ 16.5 ± 4.1 ） pg/mL and （6.5 ± 1.1 ） pg/mL, respectively. While, in the control group, the levels of IL-4 and INF-3＇ in serum were （7.3 ±1.7） pg/mL and （11.4 ± 3.3 ） pg/mL, respectively. The serum level of IL-4 in the experimental group was significantly higher than that in the control group, and there was a significant difference （P 〈 0.05）. However, the serum level of IFN-y in theexperimental group was lower than that in the control group, and there was a significant difference （P 〈 0.05）. The T-bet/GATA-3 protein expression ratio in the control group （0.62 ± 0.17 ） was significantly higher than that in the experimental group （0.12±0.03） （P 〈 0.05）. [Conclusion] Tissue remodeling exists in nasal mueosa of the allergic rhinitis mouse model, which may be relevant with the downstream Thl/Th2 immune balance disorder and IL-4/IFN-ydysseeretosis caused by transcription factors T-bet/GATA-3 expression disbalanee.