Pathogenesis of adhesive otitis media and study of mechanism of development into the pars tensa cholesteatoma

利用原位杂交技术确定了胆脂瘤上皮细胞增殖的机制，并对培养的胆脂瘤细胞系（主要是成纤维细胞和角化细胞）进行了蛋白和基因水平的分析。利用分子生物学技术研究胆脂瘤上皮细胞的分化和凋亡，特别是蛋白激酶C对分化的影响，以及白细胞介素转换酶家族（interleukin converting enzyme family， ICE）与细胞凋亡的关系。通过比较胆脂瘤上皮、正常上皮和典型炎症性角化过度牛皮癣侵袭上皮细胞的分化标志物，特别是蛋白激酶C （PKC）的表达，分析了上皮细胞终末分化的特征。我们还将在培养细胞系中分析KGF对分化标志物或细胞生长因子的影响，以解释正常上皮分化和细胞生长抑制剂的机制，进而评估胆脂瘤保守治疗的可能性。在临床方面，为了改善术后疗效，建立治疗方案，分析手术表现，明确胆脂瘤的发病机制，并比较各手术方式的治愈率。同时观察中耳炎伴积液及鼓膜粘连患者中耳膜气体交换水平及气体交换引起的中耳气压变化。在体外研究中，通过正常中耳粘膜的氧气吸入，以及药物引起的血流动力学变化相关的气体交换，特别是中耳氧分压和总压的变化，正在对家兔进行研究。

The in situ hybridization technique has been used to determine the mechanism of epithelial proliferation in cholesteatoma, and cultured cell lines, mainly of fibroblasts and keratinocytes, have been analyzed at the protein and gene level. Differentiation and apoptosis of the epithelial cells of cholesteatomas, particularly the effect of protein kinase C on differentiation, and the relationship between the interleukin converting enzyme family (ICE) and apoptosis are being investigated using molecular biological techniques.The characteristics of terminal differentiation in epithelial cells have been analyzed by comparing the expression of differentiation markers for epithelium cells, especially focusing on protein kinase C (PKC), between cholesteatomatous epithelium, normal epithelium, and the epithelium invaded by psoriasis, a typical inflammatory hyperkeratosis.The influence of KGF on differentiation markers or cell growth factors will also be analyzed in cultured cell lines to explain the mechanism of normal epithelial differentiation and cell growth inhibitors, and then to assess the possibility of conservative therapy for cholesteatoma.In the clinical field, to improve postoperative outcome and establish therapeutic procedures, surgical findings were analyzed to clarify the pathogenesis of cholesteatoma, and the improvement rates in response to each surgical procedure were compared.In addition, the level of gas exchange through the middle ear membranes and changes in middle ear pneumatic pressure according to gas exchange were examined in patients with otitis media with effusion and eardrum adhesions. In in vitro studies, oxygen inhalation through the normal middle ear mucosa, and gas exchange associated with changes in hemodynamics caused by drugs, particularly changes in partial pressure of oxygen and changes in total pressure in the middle ear are being examined in rabbits.