Department of Otology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8643-8648. doi: 10.3892/mmr.2017.7684. Epub 2017 Oct 2.
Previous studies have suggested that macrophage migration inhibitory factor (MIF) serves an important role in hearing function; however, the underlying mechanism remains unclear. In the present study, perivascular‑resident macrophage‑like melanocytes (PVM/Ms) from the stria vascularis of the lateral cochlear wall in young and aged mice were isolated. The mRNA and protein expression levels of MIF were determined using reverse transcription‑quantitative polymerase chain reaction analysis, and western blotting, respectively. MIF expression was knocked down in vitro and in vivo using small interfering RNA. Cell viability was determined using an MTT assay and cell apoptosis was determined using flow cytometry analysis. The hearing ability was assessed through the auditory brain stem response in vivo. The results of the current study demonstrated that the expression of MIF was significantly downregulated in aged mice compared with in young mice. Furthermore, the viability of PVM/Ms in aged mice was significantly decreased and the number of apoptotic PVM/Ms was significantly increased compared with that in young mice. Further studies demonstrated that the MIF knockdown accentuated hearing loss in young mice as compared with the scramble control group. In addition, the MIF knockdown in PVM/Ms significantly inhibited cell viability and lead to a significant increase in the apoptotic cell number as compared with the control group. In summary, these results revealed that the MIF knockdown significantly accentuates hearing loss in young mice in vivo, and significantly inhibits the viability and induces the apoptosis of PVM/Ms in vitro. Thus, the results of the present study may provide a novel potential therapeutic approach and prevention method for presbycusis.
先前的研究表明，巨噬细胞移动抑制因子（MIF）在听力功能中起着重要作用；然而，其潜在机制尚不清楚。在本研究中，从年轻和老年小鼠耳蜗外侧壁血管纹的血管周驻留的巨噬细胞样黑素细胞（PVM/Ms）中分离出。使用逆转录-定量聚合酶链反应分析和 Western blot 分别测定 MIF 的 mRNA 和蛋白表达水平。使用小干扰 RNA 在体外和体内敲低 MIF 表达。通过 MTT 测定法测定细胞活力，通过流式细胞术分析测定细胞凋亡。通过体内听觉脑干反应评估听力能力。本研究的结果表明，与年轻小鼠相比，老年小鼠中 MIF 的表达显著下调。此外，与年轻小鼠相比，老年小鼠中 PVM/Ms 的活力显著降低，凋亡的 PVM/Ms 数量显著增加。进一步的研究表明，与 scramble 对照组相比，MIF 敲低加重了年轻小鼠的听力损失。此外，与对照组相比，MIF 敲低显著抑制 PVM/Ms 的细胞活力，并导致凋亡细胞数量显著增加。综上所述，这些结果表明，MIF 敲低显著加重了年轻小鼠体内的听力损失，并显著抑制了 PVM/Ms 的活力并诱导其凋亡。因此，本研究的结果可能为 presbycusis 提供一种新的潜在治疗方法和预防方法。
