Trune D R, Kempton J B
Oregon Hearing Research Center, Mail Code NRC04, Department of Otolaryngology, Head and Neck Surgery, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, 97201-3098, Portland, OR, USA.
Hear Res. 2001 May;155(1-2):9-20. doi: 10.1016/s0378-5955(01)00240-4.
Recently this laboratory showed aldosterone, a mineralocorticoid that only enhances sodium transport, was as effective as the glucocorticoid prednisolone in restoring cochlear function in autoimmune mice. To further test this relationship between sodium transport and autoimmune hearing loss, dosage comparisons were made of prednisolone and aldosterone control of the auditory dysfunction in autoimmune MRL/MpJ-Fas(lpr) mice. Mice were tested at 2 months of age to establish baseline auditory brainstem response (ABR) thresholds, hematocrit, serum immune complexes, and anti-nuclear antibodies. Mice were then given different doses of prednisolone or aldosterone in their drinking water for 2 months. After the treatment period, most untreated water controls showed elevation of ABR thresholds due to the ongoing autoimmune disease. However, the steroid groups had significantly more mice with improved or unchanged thresholds. Both steroids improved stria vascularis morphology, although aldosterone appeared to be more effective. The immune suppressive prednisolone caused a dose-related improvement in levels of serum immune complexes and hematocrit, hallmarks of systemic autoimmune disease. Aldosterone, which has no immune suppressive function, did not alter systemic disease. The comparable efficacy of prednisolone and aldosterone in restoring auditory function suggests steroid reversal of autoimmune hearing loss in mice is due to increasing stria vascularis sodium transport and not suppression of systemic autoimmune reactions.
最近，本实验室发现，醛固酮（一种仅增强钠转运的盐皮质激素）在恢复自身免疫性小鼠的耳蜗功能方面与糖皮质激素泼尼松龙同样有效。为了进一步测试钠转运与自身免疫性听力损失之间的这种关系，对泼尼松龙和醛固酮在自身免疫性MRL/MpJ-Fas(lpr)小鼠中对听觉功能障碍的控制进行了剂量比较。在小鼠2个月大时进行测试，以确定基线听觉脑干反应（ABR）阈值、血细胞比容、血清免疫复合物和抗核抗体。然后，给小鼠在饮用水中给予不同剂量的泼尼松龙或醛固酮，持续2个月。治疗期结束后，由于自身免疫性疾病的持续发展，大多数未处理的饮水对照组的ABR阈值升高。然而，使用类固醇的组中，ABR阈值改善或未改变的小鼠明显更多。两种类固醇都改善了血管纹的形态，尽管醛固酮似乎更有效。具有免疫抑制作用的泼尼松龙使血清免疫复合物水平和血细胞比容呈剂量相关改善，这是系统性自身免疫性疾病的标志。而没有免疫抑制功能的醛固酮并未改变全身性疾病。泼尼松龙和醛固酮在恢复听觉功能方面的相当疗效表明，类固醇逆转小鼠自身免疫性听力损失是由于增加了血管纹的钠转运而非抑制全身性自身免疫反应。
