晚期糖基化终产物受体在小鼠耳蜗中表达的初步探讨

Expression of receptors for advanced glycation end products in mouse cochlea: a preliminary study

目的通过研究晚期糖基化终产物受体(RAGE)在小鼠耳蜗中的表达,初步探讨RAGE与老年性聋关系。方法将C57BL/6J小鼠分为2月龄、10月龄组,分别行ABR阈值检测,组织学切片观察耳蜗形态结构,免疫组化和realtime PCR检测RAGE在耳蜗中的定位和定量表达,半定量RT-PCR检测其配体S100B在耳蜗中的表达情况。结果 :(1)10月龄小鼠较2月龄ABR阈值明显提高;(2)RAGE主要在两组小鼠耳蜗的螺旋神经节细胞,内外毛细胞和血管纹中表达,10月龄C57BL/6J小鼠耳蜗中RAGE平均光密度值比2月龄小鼠大,两组间差异有统计学意义;(3)2月龄组耳蜗中RAGE相对表达量为1±0.15,10月龄组小鼠耳蜗中RAGE相对表达量为2.0816±0.117,两组间差异有统计学意义;(4)配体S100B在10月龄小鼠耳蜗中表达增高。结论 RAGE在C57BL/6J小鼠耳蜗中有表达且随年龄增大表达增强,可能与配体S100B相互作用导致听力下降,提示RAGE可能与老年性聋的发病机制有关。

Objective To study expression of receptors for advanced glycation end products （RAGE） in the cochlea and to investigate the relations between RAGE and presbyacusis. Methods Auditory brainstem response （ABR） thresholds were recorded and compared between 2 months-old and 10 months-old C57BL/6j mice. Histological sections were examined for cochlea morphology. Immunohistochemical and real time PCR methods were used to measure expression and location of RAGE in the cochlea. Semi-quantitative rt-PCR was used to measure expression of the S100B RAGE ligand in the cochlea. Result （1） ABR sensitivity in 10 months-old mice was significantly decreased compared to 2 months-old mice.（2） RAGE expression was seen mainly in spiral ganglion cells, inner hair cells, outer hair cells, and stria vascularis. Mean RAGE optical density in 10 months old mice was higher than that in 2 months old mice （p0.05）. （3） Relative expression of RAGE mRNA in the cochlea was 1 ± 0.15 in 2 months-old mice, and 2.0816 ± 0.117 in 10 months-old mice （p0.05）. （4） S100B expression was higher in 10 months-old mice. Conclusion RAGE expression is present in the cochlea and increases with age, which may interact with its ligand S100B and lead to hearing decline. The results indicate the possibility that RAGE participates in presbyacusa pathogenesis.