*Department of Otolaryngology-Head and Neck Surgery, Elazığ Military Hospital; †Department of Otolaryngology-Head and Neck Surgery, Gulhane Military Medical Academy, Ankara; ‡Department of Otolaryngology-Head and Neck Surgery, Anadolu Medical Center, Kocaeli; and §Department of Pathology, Gulhane Military Medical Academy, Ankara, Turkey.
Otol Neurotol. 2014 Jan;35(1):e15-23. doi: 10.1097/MAO.0b013e3182a0046e.
To investigate roles of types of inflammation, inducible nitric oxide synthase (iNOS), osteopontin (OPN), and calcium sensing receptor (CaSR) in the tympanic membrane and middle ear in etiopathogenesis of myringosclerosis/tympanosclerosis (MT).
Etiopathogenesis of myringosclerosis/tympanosclerosis is still unclear. Clinical and experimental observations demonstrate that hyperoxygenation might induce tympanosclerosis.
Seventy-five rats were divided into 3 groups: ventilation tube (VT) insertion, the Eustachian tube (ET) obliteration, and both procedures. Right ears were selected for mentioned interventions. Left ears served as controls. Then, histopathologic and immunohistochemical investigations were performed in tympanic bulla. MT and inflammation in tympanic membrane and middle ear space were investigated. Immunohistochemical investigation included staining with iNOS, OPN, and CaSR.
Overall 42.7% of all rats developed MT. There was no significant difference in MT incidence among the groups (ET + VT group: 56%; ET group: 44%; VT group: 28%; p > 0.017). iNOS expression occurred in 30.6% of the intervention groups with insignificant differences (ET + VT group: 40%; ET group:36%; VT group:16%; p > 0.05). There was no significant difference in iNOS expression between tympanosclerotic (25%) and non tympanosclerotic ears (34.9%) (p = 0.359). OPN was expressed in 82.6% overall. It was the highest for ET group and ET + VT group (92% for each) followed by VT group (64%). There was a marginal significance in comparison of OPN staining between VT group and ET group and also between VT group and ET + VT group (p = 0.017). There was a significant difference in OPN expression between tympanosclerotic (100%) and nontympanosclerotic ears (69.8%) (p = 0.001). Neither control ears nor intervention groups showed CaSR expression. Comparisons of inflammation of the tympanic membrane and middle ear space between tympanosclerotic and non-tympanosclerotic ears yielded significant differences (p = 0.003, p = 0.002, respectively). Tympanosclerotic ears had a tendency to show chronic or mixed inflammation in contrast to non-tympanosclerotic ears (p < 0.017). Filled-middle ear space was seen in 25% of the intervention groups with no significant difference (p > 0.017). There was a significant difference in the incidence between tympanosclerotic (46.8%) and non-tympanosclerotic ears (7%) (p < 0.017).
Based on these findings, iNOS may not be evident in stage of MT. OPN staining is strongly associated with the development of MT. CaSR has no role in formation of MT. The results proved roles of mixed or chronic inflammation and the presence of the filled-middle ear in development of MT.
研究不同类型的炎症、诱导型一氧化氮合酶 (iNOS)、骨桥蛋白 (OPN) 和钙敏感受体 (CaSR) 在鼓膜和中耳在中耳硬化症/鼓室硬化症 (MT) 发病机制中的作用。
中耳硬化症/鼓室硬化症的发病机制仍不清楚。临床和实验观察表明，高氧可能会导致鼓室硬化症。
75 只大鼠分为 3 组：通气管 (VT) 插入、咽鼓管 (ET) 阻塞和两者同时进行。右耳接受上述干预，左耳作为对照。然后在鼓室进行组织病理学和免疫组织化学检查。研究鼓膜和中耳腔的 MT 和炎症。免疫组织化学研究包括用 iNOS、OPN 和 CaSR 进行染色。
所有大鼠中有 42.7%发生了 MT。各组 MT 发生率无显著差异（ET+VT 组：56%；ET 组：44%；VT 组：28%；p>0.017）。干预组中 iNOS 表达发生率为 30.6%，无显著差异（ET+VT 组：40%；ET 组：36%；VT 组：16%；p>0.05）。在鼓室硬化（25%）和非鼓室硬化（34.9%）耳之间，iNOS 表达无显著差异（p=0.359）。OPN 总体表达率为 82.6%。ET 组和 ET+VT 组最高（各为 92%），其次是 VT 组（64%）。VT 组与 ET 组和 VT 组与 ET+VT 组之间的 OPN 染色比较有显著差异（p=0.017）。OPN 表达在鼓室硬化（100%）和非鼓室硬化耳（69.8%）之间有显著差异（p=0.001）。对照耳和干预组均未显示 CaSR 表达。在鼓膜和中耳腔炎症方面，鼓室硬化与非鼓室硬化耳之间存在显著差异（p=0.003，p=0.002）。与非鼓室硬化耳相比，鼓室硬化耳倾向于表现为慢性或混合性炎症（p<0.017）。干预组中 25%出现中耳填充，无显著差异（p>0.017）。在鼓室硬化（46.8%）和非鼓室硬化耳（7%）之间，鼓室硬化的发生率有显著差异（p<0.017）。
根据这些发现，iNOS 在 MT 阶段可能不明显。OPN 染色与 MT 的发生有很强的相关性。CaSR 在 MT 的形成中没有作用。这些结果证明了混合性或慢性炎症和中耳充满的作用在 MT 的发展中。
