神经生长因子对哮喘小鼠肺组织γ-氨基丁酸A受体表达的影响

摘要

Objective: To observe the effects of the nerve growth factor ( NGF ) on γ-amminobutyric acid type A receptor ( GABAAR) expression in lung tissue of asthmatic mice, and to explore new ideas for prevention and treatment of asthma. Methods: Thirty BALB/c mice were randomized into 3 groups(n = 10) : normal control group, the asthma group, the NGF-blocking group. We used a murine model of asthma induced by sensitized and challenged with ovalbumin. The NGF-blocking group was treated 3 h before each allergen challenge with 50 u.1 anti-NGF ( 1: 50 ). The pathological changes of the lung tissues were detected by HE staining. GABAARa, MUC5AC mRNA and protein in lung tissues were analyzed by RT-PCR and immunohistochemistry. Results: Compared with nomal control group, HE staining showed shedding epithelial cells and increasing infiltration of inflammatory cells in the asthma group. Those pathological changes of the NGF-blocking group were alleviated than the asthma group. The expression of GABAARa, MUC5AC protein and mRNA in the asthma group were higher than those of normal control group and NGF-blocking group (P <0.05) , and those in NGF-blocking group were lower than asthma group (P < 0.05). Conclusion: Anti-NGF could inhibit the expression of GABAARa and MUC5AC, and it may play a role in the treatment of excessive mucus production through down-regulating the expression of GABAARa.%目的:观察神经生长因子(NGF)对哮喘小鼠肺组织γ-氨基丁酸A受体(GABAAR)表达的影响,探讨防治哮喘新方法.方法:30只小鼠被随机分为3组:对照组、哮喘组和NGF阻断组,每组10只.以卵白蛋白(OVA)致敏激发制作哮喘小鼠模型,NGF阻断组于每次激发前3小时,先经鼻滴人抗小鼠β-NGF抗体.HE染色观察气道病理改变,用免疫组化SP法、RT-PCR法检测肺组织GABAARα、MUC5AC蛋白和mRNA的表达水平.结果:与对照组比较,哮喘组小鼠上皮细胞脱落、炎症细胞浸润增多,NGF阻断组上述病变均较哮喘组减轻,哮喘组小鼠肺组织GABAARα、MUC5AC蛋白和mRNA表达水平均较对照组高(P均＜0.05),NGF阻断组均较哮喘组降低(P均＜0.05),但仍高于对照组(P均＜0.05).结论:NGF抗体能够抑制哮喘时气道GABAARα、MUC5AC的表达,可能通过下调GABAARα的表达在哮喘气道黏液过度分泌中起治疗作用.