脂质体介导NT-3基因转染对离体小鼠耳蜗细胞的保护作用研究

发布时间：2018-06-11 22:47

本文选题：Corti氏器 + 螺旋神经节细胞　；参考：《中南大学》2010年博士论文

【摘要】：耳蜗毛细胞与螺旋神经节细胞是维持正常听力的关键细胞。耳蜗缺血、缺氧、噪声损伤和耳毒性药物等伤害性因素可对它们造成不同程度的损伤而引起感音神经性耳聋,后者是导致听力残疾的重要原因,且发病率较高,目前仍无有效治疗手段。众多研究证实,多种神经营养因子如神经营养素3(Neurotrophin 3,NT-3)对早期感音神经性耳聋有一定的疗效。但由于神经营养因子昂贵且在体内容易降解,加之耳蜗是一个高度精密的密闭的电生理器官,不宜反复进行有创性给药,一次性给药后即能维持较长时间的基因治疗方式就成为其首选。另一方面,由于缺乏理想的安全、高效的基因载体和合适的基因转染途径,内耳基因治疗研究迄今仍停留在实验室阶段,一些有关基因转染后分布、代谢、转染效率和生物安全性等问题,仍需进行大量的体外研究。本研究选用新生C57/BL-6J小鼠,对耳蜗螺旋神经节细胞与Corti器进行原代培养；以新型脂质体LipofectamineTM LTXPLUS为载体向靶细胞与靶器官转染NT-3基因,研究目的基因在螺旋神经节细胞与Corti器的表达及其对耳蜗螺旋神经节细胞生长的影响；同时研究NT-3基因的表达产物对庆大霉素所致螺旋神经节细胞与Corti器毛细胞损伤的保护作用,为内耳基因治疗提供实验依据。
[Abstract]:cochlear hair cells and spiral ganglion cells are the key cells in the maintenance of normal hearing . Injury factors such as cochlear ischemia , hypoxia , noise injury and ototoxic drugs can cause sensorineural deafness due to different degrees of injury , which is an important cause of hearing disability , and has a higher incidence , and there is still no effective treatment .

Many studies have shown that various neurotrophic factors , such as neurotrophin 3 ( NT - 3 ) , have a certain therapeutic effect on early sensorineural deafness . However , due to the fact that the neurotrophic factor is expensive and easy to degrade in vivo , the cochlear is a highly precise closed electrophysiologic organ .

In this study , newborn C57 / BL - 6J mice were selected for primary culture of cochlear spiral ganglion cells and Corti .
The NT - 3 gene was transfected into target cells and target organs by Lipofectamine TM LTXPLUS . The expression of target gene in spiral ganglion cells and Corti and its effect on the growth of cochlear spiral ganglion cells were studied .
At the same time , the protective effect of the expression product of NT - 3 gene on the damage of spiral ganglion cells and Corti ' s hair cells caused by gentamicin was studied , which provided experimental basis for the gene therapy of inner ear .
【学位授予单位】：中南大学
【学位级别】：博士
【学位授予年份】：2010
【分类号】：R764

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