Clinkard David, Amoodi Hosam, Kandasamy Thileep, Grewal Amandeep S, Chen Stephen, Qian Wei, Chen Joseph M, Harrison Robert V, Lin Vincent Y W
Sunnybrook Health Sciences Centre, Otolaryngology/Head & Neck Surgery, Toronto, Canada M4N 3M5.
ISRN Otolaryngol. 2013 Jun 27;2013:430625. doi: 10.1155/2013/430625. Print 2013.
Introduction. Previous work has shown a strong association between alterations in cochlear vasculature, aging, and the development of presbycusis. The important role of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1 in angiogenesis suggests a potential role for involvement in this process. The aim of this study was to characterize vascular structure and VEGF and its' receptors in young and old C57 Mice. Methods. Young (4 weeks, n = 14) and aged (32-36 weeks, n = 14) C57BL/6 mice were used. Hearing was evaluated using auditory brainstem response. Cochleas were characterized with qRT-PCR, immunohistochemistry, and gross histological quantification. Results. Old C57 mice demonstrated significantly decreased strial area, blood vessel number, luminal size, and luminal area normalized to strial area (vascularity). qRT-PCR showed a significant upregulation of Flt-1, a VEGF receptor, in older animals. No differences were found in VEGF-A or Flk-1. Immunohistochemistry did not show any differences in staining intensity or area with age or cochlear turn location. Conclusion. The marked deafness of aged C57 mice could be in part meditated by loss of vascular development and alterations in VEGF signaling.
引言。先前的研究表明,耳蜗血管系统的改变、衰老与老年性聋的发生之间存在密切关联。血管内皮生长因子(VEGF)及其受体Flt-1和Flk-1在血管生成中的重要作用提示其可能参与了这一过程。本研究的目的是对年轻和老年C57小鼠的血管结构、VEGF及其受体进行特征描述。方法。使用年轻(4周龄,n = 14)和老年(32 - 36周龄,n = 14)的C57BL/6小鼠。通过听性脑干反应评估听力。采用qRT-PCR、免疫组织化学和大体组织学定量对耳蜗进行特征描述。结果。老年C57小鼠的血管纹面积、血管数量、管腔大小以及相对于血管纹面积的管腔面积(血管化程度)均显著降低。qRT-PCR显示老年动物中VEGF受体Flt-1显著上调。VEGF-A或Flk-1未发现差异。免疫组织化学未显示染色强度或面积随年龄或耳蜗转位置的变化存在差异。结论。老年C57小鼠明显的耳聋可能部分是由于血管发育丧失和VEGF信号改变所致。