Mechanismofboneresorption inmiddleearcholesteatoma inthe light of H^+ concentration and H^+-sensing Proteins

目的：胆脂瘤骨吸收的发病机制尚不清楚。我们研究了中耳胆脂瘤组织的pH值和胆脂瘤上皮的通透性，试图阐明这种疾病的骨吸收机制。方法：收集原发性获得性中耳胆脂瘤患者的胆脂瘤组织。用pH计测定胆脂瘤角蛋白碎片的pH值。在激光共聚焦扫描显微镜和透射电镜下观察胆脂瘤上皮。荧光免疫组化和定量逆转录聚合酶链反应检测聚丝蛋白在胆脂瘤组织中的表达。结果：胆脂瘤角蛋白碎片pH值呈酸性。胆脂瘤上皮基底层的pH值明显低于胃窦黏膜。透射电镜显示，在胆脂瘤上皮的基层、棘层和颗粒层的细胞间隙中有明显的镧渗透，而正常皮肤的颗粒层中只有少量镧。聚丝蛋白nlRNA在胆脂瘤组织中的表达明显低于正常皮肤。结论：这些结果表明，通过胆脂质上皮的酸渗漏可能参与了底层骨结构的吸收。胆脂瘤上皮细胞通透性的增加可能与聚丝蛋白表达的减少有关。

Objective:The etiopathology of bone resorption in cholesteatoma is unclear. We studied pH inmiddle ear cholesteatoma tissue and the permeability of the cholesteatoma epithelium in an attempt to elucidate the mechanism of bone resorption in this disease.Methods:Cholesteatoma tissue was collected from patients with primary acquired middle ear cholesteatoma. The pH of the keratin debris of cholesteatoma was measured using a pH meter. The cholesteatoma epithelium was examined under a confocal laser scanning microscope, and under a transmission electron microscope. Expression of filaggrin in the cholesteatoma tissue was explored by fluorescence immunohistochemistry and by quantitative reverse transcription-polymerase chain reaction.Results: The pH of the keratin debris of cholesteatoma was acidic. The pH of the basal layer of the cholesteatoma epithelium was significantly lower than that of the antrum mucosa. Transmission electron microscope showed distinct penetration of lanthanum in the intercellular space of the basal, spinous and granular layers of the cholesteatoma epithelium, but only a small amount of lanthanum in the granular layer in the normal skin. The expression of filaggrin nlRNA was significantly lower in the cholesteatoma tissue than in the normal skin.Conclusions: These results indicate that acid leakage through the cholesteatonla epitheliunl probably participates in the resorption of the underlying bone structure. The increased permeability of the cholesteatoma epitheliunl may be explained by a decrease in filaggrin expression.