Trune Dennis R, Kempton J Beth, Harrison Andrew R, Wobig John L
Oregon Hearing Research Center, Department of Otolaryngology - Head and Neck Surgery, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA.
Hear Res. 2007 Apr;226(1-2):209-17. doi: 10.1016/j.heares.2006.09.011. Epub 2006 Nov 13.
Glucocorticoids are effective in reversing hearing loss, but their severe side effects limit long term management of many ear disorders. A clearer understanding of these side effects is critical for prolonged therapeutic control of hearing and vestibular dysfunction. Therefore, this study characterized the impact of the glucocorticoid prednisolone on cochlear dysfunction and systemic organ systems in C3.MRL-Fas(lpr) autoimmune mice and their normal C3H/HeJ parent strain. Following 3 months of treatment, autoimmune mice had better auditory thresholds and improved hematocrits, anti-nuclear antibodies, and immune complexes. Steroid treatment also lowered body and spleen weights, both of which rise with systemic autoimmune disease. Steroid treatment of the normal C3H/HeJ mice significantly elevated their blood hematocrits and lowered their body and spleen weights to abnormal levels. Thus, systemic autoimmune disease and its related hearing loss in C3.MRL-Fas(lpr) mice are steroid-responsive, but normal hemopoiesis and organ functions can be significantly compromised. This mouse model may be useful for studies of the detrimental side effects of steroid treatments for hearing loss.
糖皮质激素可有效逆转听力损失,但其严重的副作用限制了许多耳部疾病的长期治疗。更清楚地了解这些副作用对于长期治疗听力和前庭功能障碍至关重要。因此,本研究描述了糖皮质激素泼尼松龙对C3.MRL-Fas(lpr)自身免疫小鼠及其正常C3H/HeJ亲本品系的耳蜗功能障碍和全身器官系统的影响。经过3个月的治疗,自身免疫小鼠的听觉阈值更低,血细胞比容、抗核抗体和免疫复合物得到改善。类固醇治疗还降低了体重和脾脏重量,这两者都会随着全身性自身免疫疾病而增加。对正常C3H/HeJ小鼠进行类固醇治疗会显著提高其血液血细胞比容,并将其体重和脾脏重量降低到异常水平。因此,C3.MRL-Fas(lpr)小鼠的全身性自身免疫疾病及其相关的听力损失对类固醇有反应,但正常的造血和器官功能可能会受到显著损害。这种小鼠模型可能有助于研究类固醇治疗听力损失的有害副作用。