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听力损失的新型疗法:使用明胶水凝胶将胰岛素样生长因子1递送至耳蜗。

Novel therapy for hearing loss: delivery of insulin-like growth factor 1 to the cochlea using gelatin hydrogel.

作者信息

Lee Kyu Yup, Nakagawa Takayuki, Okano Takayuki, Hori Ryusuke, Ono Kazuya, Tabata Yasuhiko, Lee Sang Heun, Ito Juichi

机构信息

Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

出版信息

Otol Neurotol. 2007 Oct;28(7):976-81. doi: 10.1097/MAO.0b013e31811f40db.

Abstract

HYPOTHESIS

Local application of recombinant human insulin-like growth factor 1 (rhIGF-1) via a biodegradable hydrogel after onset of noise-induced hearing loss (NIHL) can attenuate functional and histologic damage.

BACKGROUND

The biodegradable gelatin hydrogel makes a complex with drugs by static electric charges and releases drugs by degradation of gelatin polymers. We previously demonstrated the efficacy of local rhIGF-1 application via hydrogels before noise exposure for prevention of NIHL.

METHODS

First, we used an enzyme-linked immunosorbent assay to measure human IGF-1 concentrations in the cochlear fluid after placing a hydrogel containing rhIGF-1 onto the round window membrane of guinea pigs. Second, the functionality and the histology of guinea pig cochleae treated with local rhIGF-1 application at different concentrations after noise exposure were examined. Control animals were treated with a hydrogel immersed in physiologic saline alone.

RESULTS

The results revealed sustained delivery of rhIGF-1 into the cochlear fluid via the hydrogel. The measurement of auditory brainstem responses demonstrated that local rhIGF-1 treatment significantly reduced the threshold elevation from noise. Histologic analysis exhibited increased survival of outer hair cells by local rhIGF-1 application through the hydrogel.

CONCLUSION

These findings indicate that local rhIGF-1 treatment via gelatin hydrogels is effective for treatment of NIHL.

摘要

假设

在噪声性听力损失(NIHL)发作后,通过可生物降解水凝胶局部应用重组人胰岛素样生长因子1(rhIGF-1)可减轻功能和组织学损伤。

背景

可生物降解的明胶水凝胶通过静电荷与药物形成复合物,并通过明胶聚合物的降解来释放药物。我们之前已经证明在噪声暴露前通过水凝胶局部应用rhIGF-1对预防NIHL的有效性。

方法

首先,我们将含有rhIGF-1的水凝胶放置在豚鼠圆窗膜上后,使用酶联免疫吸附测定法测量耳蜗液中的人IGF-1浓度。其次,检查噪声暴露后用不同浓度的局部rhIGF-1处理的豚鼠耳蜗的功能和组织学。对照动物仅用浸入生理盐水的水凝胶处理。

结果

结果显示rhIGF-1通过水凝胶持续递送至耳蜗液中。听觉脑干反应的测量表明,局部rhIGF-1治疗显著降低了噪声引起的阈值升高。组织学分析显示通过水凝胶局部应用rhIGF-1可增加外毛细胞的存活率。

结论

这些发现表明通过明胶水凝胶局部应用rhIGF-1对治疗NIHL有效。

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