Toll样受体在慢性化脓性中耳炎和中耳胆脂瘤中的差异表达及其意义

Differential expression of toll-like receptors in chronic suppurative otitis media and cholesteatoma

目的检测Toll样受体2（toll—likereceptor2，TLR2）和Toll样受体4（toll—likereceptor4，TLR4）在慢性化脓性中耳炎、中耳胆脂瘤中的表达，探讨其在慢性化脓性中耳炎和中耳胆脂瘤发病中的作用。方法选取耳硬化症患者（对照组）、慢性化脓性中耳炎患者（化脓性中耳炎组）、中耳胆脂瘤患者（中耳胆脂瘤组）各30例，应用实时定量聚合酶链反应（real—timePCR）、蛋白质印迹法（Westernblot）、免疫组化检测TLR2／TLR4在正常外耳道皮肤，慢性化脓性中耳炎黏膜、肉芽组织，中耳胆脂瘤患者黏膜、肉芽组织及胆脂瘤囊壁中的表达，并比较表达程度的差异。结果@TLR2／TLR4mRNA及蛋白质在正常外耳道皮肤，慢性化脓性中耳炎中耳黏膜、肉芽组织，胆脂瘤的中耳黏膜、肉芽组织及胆脂瘤囊壁均有表达。@TLR2／TLR4mRNA及其蛋白质在慢性化脓性中耳炎及胆脂瘤黏膜中的表达均高于正常外耳道皮肤（P值均〈0．05），在胆脂瘤囊壁中的表达低于正常外耳道皮肤（P值均〈0．05），两组黏膜中TLR2／TLR4的表达差异无统计学意义（P值均〉0．05）。③TLR2／TLR4mRNA及蛋白质在两组中耳炎肉芽组织中的表达均高于正常外耳道皮肤（P值均〈0．01），且TLR2mRNA在中耳胆脂瘤肉芽组织中的表达高于慢性化脓性中耳炎（P〈0．05）。④TLR2／TLR4阳性细胞主要分布在肉芽组织中，且明显多于正常外耳道皮肤，但胆脂瘤囊壁中的阳性细胞少于正常外耳道皮肤。结论TLR2和TLR4在正常外耳道皮肤、慢性化脓中耳炎及中耳胆脂瘤中均有表达，提示中耳具有TLR2、TLR4参与调节的固有免疫系统，但二者的差异性表达也提示其在慢性化脓性中耳炎和中耳胆脂瘤的发病中所起的作用不同。

Objective To investigate the differential expression of toll-like receptor 2 （TLR2）, toll-like receptor 4 （TLR4） and their potential role in the pathogenesis of chronic suppurative otitis meida and cholesteatoma. Methods Normal cannal skin of 30 patients with tympanosclerosis were enrolled as control, 30 cases with choronic suppurative otitis media and 30 patients with cholesteatoma were studied. Real-time PCR, Western blot and Immunohistochemistry were preformed to detect the expression of TLR2/TLR4 in normal canal skin, mucosa and granulation tissue of choronic suppurative otitis media, mucosa, granulation tissue, cholesteatoma epithelium of cholesteatoma, and the differential expression were ananlyzed. Results （1）the mRNA and protein expression of TLR2 and TLR4 were detected in all normal canal skin, mucosa and granulation tissue of choronic suppurative otitis media, mucosa, granulation tissue, cholesteatoma epithelium of cholesteatoma. （2）Both mRNA and protein level of TLR2/TLR4 in mucosa of chronic suppurative otitis media and cholesteatoma were higher than those in normal canal skin, but lower in cholesteatoma epithelium, there was no significant difference in mucosa of the two otitis media groups. （3）The mRNA and protein expressiom of TLR2/TLR4 in granulation tissue of chronic suppurative otitis media and cholesteatoma were significant increased when compared with normal canal skin, and TLR2 expression level was higher in granulation tissue of cholesteatoma than in choronic suppurative otitis meida. （4）TLR2/TLR4 positive ceils mainly infiltrated in granulations, significantly more than in normal skin, while fewer in the epithelium of cholesteatoma. Conclusions Differential expression of TLR2 and TLR4 in mucosa suggests middle ear is a TLR2/TLR4 participated functional modulation of the innate immune system and also suggests that they may play a different role in the pathophysiology of chronic otitis media and cholesteatoma.