Chen Guan-Gui, Mao Min, Qiu Li-Zi, Liu Qi-Ming
Department of Otorhinolaryngology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China.
Neural Regen Res. 2015 Mar;10(3):425-31. doi: 10.4103/1673-5374.153691.
Polyethyleneimine-polyethylene glycol (PEI-PEG), a novel nanocarrier, has been used for transfection and gene therapy in a variety of cells. In our previous study, we successfully carried out PEI-PEG-mediated gene transfer in spiral ganglion cells. It remains unclear whether PEI-PEG could be used for gene therapy with X-linked inhibitor of apoptosis protein (XIAP) in the inner ear. In the present study, we performed PEI-PEG-mediated XIAP gene transfection in the cochlea of Sprague-Dawley rats, via scala tympani fenestration, before daily cisplatin injections. Auditory brainstem reflex tests demonstrated the protective effects of XIAP gene therapy on auditory function. Immunohistochemical staining revealed XIAP protein expression in the cytoplasm of cells in the spiral ganglion, the organ of Corti and the stria vascularis. Reverse transcription-PCR detected high levels of XIAP mRNA expression in the cochlea. The present findings suggest that PEI-PEG nanocarrier-mediated XIAP gene transfection results in XIAP expression in the cochlea, prevents damage to cochlear spiral ganglion cells, and protects hearing.
聚乙烯亚胺-聚乙二醇（PEI-PEG）是一种新型纳米载体，已用于多种细胞的转染和基因治疗。在我们之前的研究中，我们成功地在螺旋神经节细胞中进行了PEI-PEG介导的基因转移。目前尚不清楚PEI-PEG是否可用于内耳中X连锁凋亡抑制蛋白（XIAP）的基因治疗。在本研究中，我们在每日注射顺铂之前，通过鼓膜开窗，在Sprague-Dawley大鼠的耳蜗中进行了PEI-PEG介导的XIAP基因转染。听觉脑干反应测试证明了XIAP基因治疗对听觉功能的保护作用。免疫组织化学染色显示XIAP蛋白在螺旋神经节、柯蒂氏器和血管纹细胞的细胞质中表达。逆转录-聚合酶链反应检测到耳蜗中XIAP mRNA的高水平表达。本研究结果表明，PEI-PEG纳米载体介导的XIAP基因转染导致耳蜗中XIAP的表达，防止耳蜗螺旋神经节细胞受损，并保护听力。
