Trune D R, Kempton J B, Kessi M
Oregon Hearing Research Center, Department of Otolaryngology--Head and Neck Surgery, Oregon Health Sciences University, Portland 97201-3998, USA.
Laryngoscope. 2000 Nov;110(11):1902-6. doi: 10.1097/00005537-200011000-00025.
Although the glucocorticoid prednisone is the standard therapy for autoimmune sensorineural hearing loss, what this hormone does in the ear to restore hearing is not known. MRL/MpJ-Fas(lPr) autoimmune mice consistently have shown only stria vascularis disease, implying that abnormal ion balances in the endolymph underlie cochlear dysfunction. Previously we have shown that hearing loss in these mice is reversed with prednisolone treatment. This, coupled with the complete lack of cochlear inflammation, suggests that the restoration of hearing with prednisolone is due to its sodium transport function and not to its anti-inflammatory or immune suppression effects. Therefore the hypothesis of this study was that the mineralocorticoid aldosterone, which only increases sodium transport, would be as effective as prednisolone in reversing autoimmune hearing loss.
MRL/MpJ-Fas(lPr) autoimmune mice were treated with either prednisolone or aldosterone to compare steroid effects on auditory brainstem response (ABR) thresholds and stria morphology.
After baseline ABR audiometry, autoimmune mice were given prednisolone (5 mg/kg per day), aldosterone (15 microg/kg per day), or water in their drinking bottles. After 2 months of treatment the ABR thresholds were remeasured, and ears collected for histological examination.
The untreated controls showed continued elevation of ABR thresholds and edematous stria. However, thresholds in most steroid mice were improved or unchanged and their stria morphology improved, particularly with aldosterone treatment.
Restoration of hearing with steroid treatment is due to increased sodium transport to re-establish cochlear ionic balances. Aldosterone therapy may offer advantages over prednisone for long-term management of not only autoimmune hearing loss, but also other forms of nonimmune-related deafness for which steroids are currently prescribed.
尽管糖皮质激素泼尼松是自身免疫性感音神经性听力损失的标准疗法,但这种激素在耳内恢复听力的作用尚不清楚。MRL/MpJ-Fas(lPr)自身免疫小鼠一直仅表现出血管纹疾病,这意味着内淋巴中异常的离子平衡是耳蜗功能障碍的基础。此前我们已表明,这些小鼠的听力损失可通过泼尼松龙治疗得到逆转。这一点,再加上完全没有耳蜗炎症,表明泼尼松龙恢复听力是由于其钠转运功能,而非其抗炎或免疫抑制作用。因此,本研究的假说为,仅增加钠转运的盐皮质激素醛固酮在逆转自身免疫性听力损失方面将与泼尼松龙一样有效。
用泼尼松龙或醛固酮治疗MRL/MpJ-Fas(lPr)自身免疫小鼠,以比较类固醇对听性脑干反应(ABR)阈值和血管纹形态的影响。
在进行基线ABR听力测定后,给自身免疫小鼠饮用含泼尼松龙(每天5毫克/千克)、醛固酮(每天15微克/千克)或水的溶液。治疗2个月后,重新测量ABR阈值,并收集耳朵进行组织学检查。
未治疗的对照组显示ABR阈值持续升高,血管纹水肿。然而,大多数接受类固醇治疗的小鼠的阈值有所改善或未变,其血管纹形态得到改善,尤其是接受醛固酮治疗的小鼠。
类固醇治疗恢复听力是由于钠转运增加以重新建立耳蜗离子平衡。醛固酮疗法不仅在自身免疫性听力损失的长期管理方面,而且在目前使用类固醇治疗的其他形式的非免疫性相关耳聋方面,可能比泼尼松具有优势。