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复制缺陷型腺病毒为载体的Math1基因内耳应用安全性研究

Evaluation of the Safety of Adenovirus-Math1 Administration to Inner Ear

徐金操;胡吟燕;徐延军;孙建和;黄德亮;杨仕明;

1:解放军第二炮兵总医院耳鼻咽喉头颈外科

2:解放军总医院耳鼻咽喉-头颈外科解放军耳鼻咽喉研究所

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摘要

目的研究以复制缺陷型腺病毒为载体的Math1基因内耳应用的安全性。方法将10只成年Wistar大鼠分为正常对照组和缺失E1、E3基因片段且构建有Math1基因和绿色荧光蛋白报告基因的复制缺陷型腺病毒(adenovirus-Math1-enhanced green fluorescence protein,Ad-Math1-EGFP)前庭阶导入组(实验组),每组5只,实验组大鼠在右耳通过耳蜗底回前庭阶打孔的方法导入物理滴度为2.1×1011v.p/ml的上述腺病毒5μl,对照组大鼠不做任何处理。7天后对动物进行颈髓硬膜外短声诱发电位(click-evoked potentials on the surface of the cervical dura mater,CDM-CEP)、听性脑干反应(ABR)阈值检测和游泳试验,评价前庭和耳蜗功能,然后将动物处死进行组织形态学观察。结果Ad-Math1-EGFP导入7天后,实验组大鼠前庭及耳蜗的毛细胞及纤毛均未见破坏,形态正常。短声刺激下,对照组大鼠CDM-CEP的阈值为85±3.54dBSPL,ABR阈值为37±4.47dBSPL;实验组大鼠CDM-CEP的阈值为89±6.52dBSPL,ABR阈值为40±3.54dBSPL;对照组大鼠的游泳时间为4.0±0.71s,实验组为5.0±0.71s,两组之间比较差异均无统计学意义。结论携带Math1基因的复制缺陷型腺病毒对前庭和耳蜗毛细胞是安全的,可以作为基因导入的理想载体。

关键词

Math1基因;安全性;腺病毒;内耳

基金项目(Foundation):

国家自然科学基金(面上项目30571017;30000189);; 海外青年合作基金(30628030);; 北京自然科学基金(7042061);; 国家863计划(2007AA02Z150);; 国家自然科学基金重点项目(30730040)资助

作者

徐金操;胡吟燕;徐延军;孙建和;黄德亮;杨仕明;

参考文献

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