杀菌-通透性增强蛋白对分泌性中耳炎大鼠水通道蛋白和黏蛋白表达的影响

Effects of BPI on expression of aquaporin and mucin in middle ear mucosa of rats with otitis media with effusion

目的观察杀菌-通透性增强蛋白对分泌性中耳炎模型大鼠中耳黏膜中水通道蛋白和黏蛋白表达的影响,探讨可能的作用机制。方法采用内毒素制备分泌性中耳炎大鼠模型,将70只大鼠随机分为模型组(10只)和杀菌-通透性增强蛋白(bactericidal-permeability increasing protein,BPI)组(60只),另取10只大鼠作为正常对照组,采用ELISA法检测给药后各组大鼠中耳积液中水通道蛋白AQP1、AQP4及黏蛋白MUC5B、MUC5AC水平,实时荧光定量PCR法检测各组大鼠中耳黏膜中AQP1、AQP4及MUC5B、MUC5AC mRNA的表达水平。结果模型组AQP1蛋白及mRNA表达量显著低于正常对照组,而AQP4、MUC5B、MUC5AC蛋白及mRNA表达量显著高于正常对照组(P<0.01)。经BPI治疗后,AQP1的表达升高,而AQP4、MUC5B、MUC5AC的表达降低(P<0.05或0.01)。结论 AQP1、AQP4及MUC5B、MUC5AC在分泌性中耳炎病变的形成中起一定作用;BPI通过提高AQP1,抑制AQP4及MUC5B、MUC5AC的表达和分泌,从而减轻分泌性中耳炎的积液分泌;BPI是一个潜在的治疗分泌性中耳炎的药物,可能有效预防慢性分泌性中耳炎的发生。

OBJECTIVE To study the effect of bactericidal/permeability increasing protein （BPI） on gene expression and protein levels of aquaporin and mucin in the middle ear mucosa of rat model with otitis media with effusion （OME）, and explore its possible mechanism. METHODS Seventy rats were subjected to OME by injecting endotoxin （LPS） into middle ear cavity, and animals were divided into LPS group（10 rats） and BPI group（60 rats）.AQP1, AQP4, MUC5B, and MUC5AC mRNA expression and their protein levels in middle ear effusion or mucosa were measured at various intervals by ELISA and Real-time PCR. RESULTS AQP1 mRNA expression and protein levels in LPS group were lower than that of control group, while AQP4, MUC5B, MUC5AC mRNA expressions and protein levels were higher than control group （P〈 0.01）. After BPI treatment, AQP1 mRNA expression and protein levels increased, and AQP4, MUC5B, MUC5AC expressions decreased （P〈0.05 or 0.01）. CONCLUSION AQP1, AQP4, MUC5B and MUC5AC may play an important role in the development of OME. BPI can enhance the expression and secretion of AQP1 and inhibit the expression of AQP4, MUC5B and MUC5AC, which may result in the reduction of effusion secretion. BPI may be a potential drug for OME and prevent occurrence of chronic OME .