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用于控制自身免疫性感音神经性听力损失的局部内耳基因治疗的实验研究

Experimental study of local inner ear gene therapy for controlling autoimmune sensorineural hearing loss.

作者信息

Tan Chang-qiang, Gao Xia, Cai Wen-jun, Qian Xiao-yun, Lu Ling, Huang He

机构信息

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, No. 5 Xinmofan Road, Nanjing, Jiangsu 210009, China.

Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Jiangsu 210008, China.

出版信息

Biomed Res Int. 2014;2014:134658. doi: 10.1155/2014/134658. Epub 2014 Apr 7.

DOI:10.1155/2014/134658
PMID:24804196
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3997895/
Abstract

This study aimed to investigate the efficacy of gene therapy for treating autoimmune sensorineural hearing loss (ASHL) via local administration of a recombinant adenovirus vector containing the Fas ligand or interleukin IL-10 gene. Guinea pigs were divided into four groups, with different microinjections in the scala tympani. Group A were injected with FasL-EGFP, B with IL-10-EGFP, C with EGFP, and D with artificial perilymph. Seven days later, auditory brain-stem response (ABR) was tested, and the temporal bone was stained and observed by light microscopy. The spiral ligament and basement membrane were observed using transmission electron microscopy. FasL and IL-10 expression were examined using immunofluorescence histochemistry. Immunohistochemical analysis showed that the recombinant adenovirus vector in Groups A, B, and C can transfect the stria vascularis, the spiral ligament, the organ of Corti, the spiral ganglion, the region surrounding the small blood vessel in the modiolus, and the cochlear bone wall. Compared with those in Groups C and D, the ABR wave III mean thresholds were significantly lower and the inner ear immunoinflammatory responses in Groups A and B were significantly alleviated. Inhibition of immunoinflammatory response alleviated immunoinflammatory injury and auditory dysfunction. This technique shows potential as a novel therapy for ASHL.

摘要

本研究旨在通过局部注射含Fas配体或白细胞介素IL-10基因的重组腺病毒载体，探讨基因治疗自身免疫性感音神经性听力损失（ASHL）的疗效。将豚鼠分为四组，在鼓阶进行不同的微量注射。A组注射FasL-EGFP，B组注射IL-10-EGFP，C组注射EGFP，D组注射人工外淋巴。7天后，检测听性脑干反应（ABR），对颞骨进行染色并通过光学显微镜观察。使用透射电子显微镜观察螺旋韧带和基底膜。采用免疫荧光组织化学法检测FasL和IL-10的表达。免疫组织化学分析表明，A、B、C组中的重组腺病毒载体可转染血管纹、螺旋韧带、柯蒂器、螺旋神经节、蜗轴中小血管周围区域以及耳蜗骨壁。与C组和D组相比，A组和B组的ABR波III平均阈值显著降低，内耳免疫炎症反应明显减轻。免疫炎症反应的抑制减轻了免疫炎症损伤和听觉功能障碍。该技术显示出作为ASHL新型治疗方法的潜力。

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Gene therapy for the inner ear.内耳基因治疗。
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Interleukin-10 gene-transfected mature dendritic cells suppress murine experimental autoimmune optic neuritis.白细胞介素-10 基因转染的成熟树突状细胞抑制实验性自身免疫性视神经炎。
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Microarray-based gene expression profiling reveals the mediators and pathways involved in the anti-arthritic activity of Celastrus-derived Celastrol.
基于微阵列的基因表达谱分析揭示了来源于雷公藤的雷公藤红素的抗关节炎活性所涉及的介质和途径。
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