中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (3): 425-431.doi: 0.4103/1673-5374.153691

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

叶酸复合物载体介导基因转染可减轻顺铂致耳蜗螺旋神经节细胞损害

  

  • 收稿日期:2014-11-07 出版日期:2015-03-20 发布日期:2015-03-20
  • 基金资助:

    广东省自然科学基金(博士启动)项目,编号:S2011040003553

Gene transfection mediated by polyethyleneimine-polyethylene glycol nanocarrier prevents cisplatin-induced spiral ganglion cell damage

Guan-gui Chen, Min Mao, Li-zi Qiu, Qi-ming Liu   

  1. Department of Otorhinolaryngology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China
  • Received:2014-11-07 Online:2015-03-20 Published:2015-03-20
  • Contact: Guan-gui Chen, M.D., ent2000@163.com
  • Supported by:

    This study was supported by the Natural Science Foundation of Guangdong Province in China, No. S2011040003553.

摘要:

 叶酸聚乙二醇接枝支化聚乙烯亚胺纳米载体作为新型纳米载体,已经成功应用于多种细胞的转染及基因治疗研究中,作者前期研究发现其可介导基因转染体外培养的螺旋神经节细胞,但是否可以利用这种载体进行X连锁凋亡抑制蛋白内耳基因治疗呢?实验利用叶酸聚乙二醇接枝支化聚乙烯亚胺纳米载体携带X连锁凋亡抑制蛋白基因,通过耳蜗鼓阶开窗的方式转染于顺铂损伤SD大鼠耳蜗。听性脑干反射检测结果显示X连锁凋亡抑制蛋白基因治疗对听功能有保护作用,免疫组化染色观察到螺旋神经节细胞、cotic器及血管纹等处细胞胞质内X连锁凋亡抑制蛋白蛋白表达,且RT-PCR检测到耳蜗组织X连锁凋亡抑制蛋白mRNA的高表达。说明叶酸聚乙二醇接枝支化聚乙烯亚胺纳米载体介导的X连锁凋亡抑制蛋白基因可表达于耳蜗组织,减轻顺铂对耳蜗螺旋神经节细胞损害,起到保护听力的作用。

关键词: 叶酸聚乙二醇接枝支化聚乙烯亚胺纳米载体, X连锁凋亡抑制蛋白, 基因治疗, 纳米载体, 耳蜗, 螺旋神经节细胞, 顺铂, 耳毒性

Abstract:

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.

Key words: nerve regeneration, polyethyleneimine-polyethylene glycol, spiral ganglion cells, X-linked , inhibitor of apoptosis protein, gene therapy, nanocarrier, cisplatin, neural regeneration, ototoxicity, cochlea