中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (1): 154-160.doi: 10.4103/1673-5374.224382

• 原著:颅神经损伤修复保护与再生 • 上一篇    下一篇

 SDF-1/CXCR4信号通路在噪声性听力损失大鼠耳蜗干细胞归巢中的作用

  

  • 收稿日期:2017-12-04 出版日期:2018-01-15 发布日期:2018-01-15
  • 基金资助:

    伊朗Shahid Beheshti医科大学听力障碍研究中心项目

Critical role of SDF-1/CXCR4 signaling pathway in stem cell homing in the deafened rat cochlea after acoustic trauma

Ali Asghar Peyvandi1, Navid Ahmady Roozbahany1, 2, Hassan Peyvandi1, 3, Hojjat-Allah Abbaszadeh1, 4, Niloofar Majdinasab1,Mohammad Faridan5, Somayeh Niknazar1   

  1. 1 Hearing Disorders Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
    2 G. Raymond Chang School, Ryerson University, Toronto, Canada
    3 Yale University, New Haven, CT, USA
    4 Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
    5 Department of Occupational Health Engineering, School of Health, Loorestan University of Medical Sciences, Khorramabad, Iran
  • Received:2017-12-04 Online:2018-01-15 Published:2018-01-15
  • Contact: Somayeh Niknazar, Ph.D.,niknazar.somayeh@gmail.com.
  • Supported by:

    This work was financially supported by the Hearing Disorders Research Center of Shahid Beheshti University of Medical Sciences.

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摘要：

以往的动物实验表明，骨髓间充质干细胞（bone marrow mesenchymal stem cell，BMSCs）向损伤区域迁移的过程中，基质细胞衍生因子1（SDF-1）/CXC趋化因子受体4（CXCR4）信号通路有重要作用。为研究趋化性基质细胞衍生因子1/ CXC趋化因子受体4信号通路在移植的骨髓间充质干细胞归巢至噪声性听力损失大鼠损伤耳蜗中的潜在作用。实验以5d时间内给予雄性大鼠白噪声暴露（110dB）6h的方法诱导建立听力损失模型。造模后将Hoechst 33342标记的骨髓间充质干细胞和CXC趋化因子受体4拮抗剂AMD3100处理的骨髓间充质干细胞通过圆窗注射入大鼠耳蜗。Western blot法检测耳蜗基质细胞衍生因子1蛋白表达。干细胞移植后24h计数到达内淋巴的标记骨髓间充质干细胞的数量。发现噪声致听力损失大鼠耳蜗基质细胞衍生因子1含量明显升高。噪声性听力损失大鼠耳蜗内注射经AMD3100处理的骨髓间充质干细胞后，到达内淋巴的Hoechst 33342标记骨髓间充质干细胞数量明显减少。研究结果表明基质细胞衍生因子1/ CXC趋化因子受体4信号通路在噪声性听力损失大鼠移植干的细胞迁移至耳蜗损伤区域中具有重要作用。

orcid:0000-0002-9985-2144(Somayeh Niknazar)

关键词: 神经再生, 干细胞, 细胞归巢, SDF-1/CXCR4轴, 噪声性听力损失

Abstract:

Previous animal studies have shown that stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) signaling pathway plays an important role in the targeted migration of bone marrow-derived mesenchymal stem cells (BMSCs) to the injured area. In the present study, we aimed to investigate the potential role of chemotactic SDF-1/CXCR4 signaling pathway in the homing of transplanted BMSCs to the injured cochlea after noise-induced hearing loss (NIHL) in a rat model. White noise exposure (110 dB) paradigm was used for hearing loss induction in male rats for 6 hours in 5 days. Distortion-product otoacoustic emission (DPOAE) responses were recorded before the experiment and post noise exposure.Hoechst 33342-labeled BMSCs and CXCR4 antagonist (AMD3100)-treated BMSCs were injected into the rat cochlea through the round window. SDF-1 protein expression in the cochlear tissue was assayed using western blot assay. The number of labeled BMSCs reaching the endolymph was determined after 24 hours.SDF-1 was significantly increased in the cochlear tissue of rats in the noise exposure group than in the control group. The number of Hoechst 33342-labeled BMSCs reaching the endolymph of the cochlea was significantly smaller in the AMD3100-treated BMSCs group than in the normal BMSCs group. Our present findings suggest that the SDF-1/CXCR4 signaling pathway has a critical role in BMSCs migration to the injured cochlea in a rat model of noise-induced hearing loss.

Key words: nerve regeneration, stem cells, migration, SDF-1/ CXCR4 axis, noise-induced hearing loss, neural regeneration