腺病毒介导的NT3基因转染对噪音损伤的耳蜗螺旋神经节细胞的保护作用  

Adenovirus-mediated NT3 gene transfer protects spiral ganglion neurons from degeneration after noise trauma

作　　者：陈谦[1] 郭维维[2] 吴燕[1] 刘红[1] 翟所强[2] 汪家政[1] 范明[1] 

机构地区：[1]军事医学科学院基础医学研究所,北京100850 [2]解放军总医院耳鼻喉科研究所,北京100853

出　　处：《生理学报》2002年第3期263-266,共4页Acta Physiologica Sinica

基　　金：theNationalNaturalScienceFoundationofChina (No 39770 2 5 7)

摘　　要：神经营养素 3(neurotrophin 3,NT3)作为螺旋神经节细胞特异的营养因子 ,可有效地支持内耳传入神经元的存活 ,因此有望成为治疗因其退变而引起的感音性神经性耳聋的有效因子。实验采用腺病毒介导lacZ基因 ,检测了外源基因在豚鼠内耳中的长期表达。用噪音制备了豚鼠耳聋模型 ,在噪音损伤后第 7天 ,通过圆窗膜注入 1× 10 8重组腺病毒。注入神经营养素 3重组腺 (Ad NT3)的组为实验组 ,注入Ad lacZ的为对照组。 4周后 ,经NT3抗体免疫细胞化学染色可见 ,在注入Ad NT3病毒的实验组中 ,在内耳多种细胞中有明显的NT3蛋白的表达。HE染色显示 ,注射Ad lacZ组的豚鼠耳蜗螺旋神经节细胞明显退变 ,螺旋神经节内细胞间隙拉大 ,细胞密度明显低于注射Ad NT3实验组动物 (P <0 .0 1)。这一结果说明 ,腺病毒介导的NT3基因可长期表达于内耳中 ,并且可在噪音引起毛细胞死亡后有效地抑制螺旋神经节细胞的退变。Numerous studies have shown that the health of spiral ganglion neurons is highly important for hearing. As a trophic factor of spiral ganglion neurons, neurotrophin 3 (NT3) is a potential candidate for prevention of spiral ganglion neuron degeneration in human. In our experiments, efficient transduction and long term expression of foreign gene of cochlea cells has been found with adenovirus carried lacZ gene (Ad-lacZ). A model of guinea pig deafness was made by intense noise exposure, which destroyed the entire organ of Corti in the middle part of the cochlea. Seven days after noise exposure, the animals were anesthetized and 1×10 8 recombinant adenoviral particles were injected into the scala tympani through the round window membrane. Animals inoculated with neurotrophin 3 adenovirus (Ad-NT3) were designated as the experimental group, animals inoculated with Ad-lacZ vector served as the control group. Four weeks after the inoculation of the virus, NT3 immunoreactivity was observed in the Ad-NT3 inoculated group. HE histochemical staining results showed that in the Ad-lacZ injected group, the neuronal degeneration was severer and the density of spiral ganglion neurons was significantly lower than those in the Ad-NT3 injected group. Our results demonstrate that with adenovirus-mediated overexpression NT3 may be developed into a new treatment to prevent secondary spiral ganglion degeneration following the damage to Corti organ.

关 键 词：重组腺病毒 神经营养素3 噪音 螺旋神经节 

分 类 号：R764[医药卫生—耳鼻咽喉科]