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中年和年轻成年小鼠对噪声性听力损失的易感性:CBA、C57BL和BALB近交系的剂量反应研究方法

Vulnerability to noise-induced hearing loss in 'middle-aged' and young adult mice: a dose-response approach in CBA, C57BL, and BALB inbred strains.

作者信息

Ohlemiller K K, Wright J S, Heidbreder A F

机构信息

Fay and Carl Simons Center for the Biology of Hearing and Deafness, Central Institute for the Deaf, 818 S. Euclid Av., St. Louis, MO 63110, USA.

出版信息

Hear Res. 2000 Nov;149(1-2):239-47. doi: 10.1016/s0378-5955(00)00191-x.

DOI:10.1016/s0378-5955(00)00191-x
PMID:11033262
Abstract

Vulnerability of the cochlea to noise-induced permanent threshold shifts (NIPTS) was examined in young adult (1-2 months) and 'middle-aged' (5-7 months) CBA/CaJ, C57BL/6J, and BALB/cJ inbred mice. For each age and strain, a dose-response paradigm was applied, whereby groups of up to 12 animals were exposed to intense broadband noise (110 dB SPL) for varying durations. Exposure durations reliably associated with <10% and >90% probability of a criterion amount of NIPTS (determined 2 weeks post-exposure) were identified, and the minimum NIPTS exposure and the slope of the dose-response relation were then derived by numerical modeling. For all three strains, young adult mice were more susceptible to NIPTS than older adults; That is, a shorter exposure was able to cause NIPTS in the younger mice. Strain comparisons revealed that C57 mice were more susceptible than CBAs in the older age group only. At both ages examined, however, BALB mice were most susceptible to NIPTS. When animals with a similar amount of NIPTS were compared, outer hair cell loss in the cochlear base was more widespread in the younger animals. BALB mice appear particularly susceptible to noise-induced outer hair cell loss throughout life. Our data suggest that the mechanism or site of noise injury differs between young adults and older adults, and may depend on genetic background. The finding that both BALB and C57 mice, which show pronounced age-related hearing loss, are also especially vulnerable to noise supports the notion that genes associated with age-related hearing loss often act by rendering the cochlea susceptible to insults.

摘要

在年轻成年(1 - 2个月)和“中年”(5 - 7个月)的CBA/CaJ、C57BL/6J和BALB/cJ近交系小鼠中,研究了耳蜗对噪声诱导的永久性阈值偏移(NIPTS)的易感性。对于每个年龄和品系,采用剂量反应范式,将多达12只动物的组暴露于强度宽带噪声(110 dB SPL)中不同时长。确定了与NIPTS标准量的<10%和>90%概率可靠相关的暴露时长(在暴露后2周确定),然后通过数值建模得出最小NIPTS暴露量和剂量反应关系的斜率。对于所有三个品系,年轻成年小鼠比老年小鼠对NIPTS更易感;也就是说,较短的暴露就能在年轻小鼠中引起NIPTS。品系比较显示,仅在老年组中,C57小鼠比CBA小鼠更易感。然而,在两个研究年龄中,BALB小鼠对NIPTS最易感。当比较具有相似NIPTS量的动物时,耳蜗基部外毛细胞损失在年轻动物中更广泛。BALB小鼠在一生中似乎对噪声诱导的外毛细胞损失特别易感。我们的数据表明,年轻成年人和老年人之间噪声损伤的机制或部位不同,并且可能取决于遗传背景。BALB和C57小鼠均表现出明显的年龄相关性听力损失,且对噪声也特别易感,这一发现支持了与年龄相关性听力损失相关的基因通常通过使耳蜗易受损伤而起作用的观点。

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