目的:观察玻璃体腔内注射腺病毒介导的脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)前后STZ糖尿病大鼠视网膜中酪氨酸羟化酶(tyrosine hydroxylase,TH)的水平及多巴胺能无长突细胞数目的变化。方法:选取9周龄Wistar大鼠,链脲佐菌素(streptozotocin,STZ)ip,制成糖尿病模型后2wk,玻璃体腔内注射含有BDNF基因的5型重组腺病毒(Ad.BDNF),模型建立后4wk,处死大鼠,取视网膜组织进行Western blotting及视网膜铺片免疫组织化学染色检测,观察视网膜中TH水平的变化,从而反映糖尿病大鼠视网膜中多巴胺能无长突细胞水平的变化。结果:实验组糖尿病大鼠未注射Ad.BDNF眼视网膜中TH蛋白水平降低,多巴胺能无长突细胞计数及灰度低于对照组,均有统计学差异;实验组注射Ad.BDNF眼视网膜中TH蛋白水平、多巴胺能无长突细胞计数及灰度与对照组无统计学差异。结论:STZ早期糖尿病大鼠玻璃体腔内注射Ad.BDNF可提高视网膜中TH的水平,提高多巴胺能无长突细胞的数目。

AIM:To observe the changes of tyrosine hydroxylase(TH)protein levels and the density of dopaminergic amacrine cells before and after the administration of adenovirus-mediated brain-derived neurotrophic factor(Ad.BDNF)into the vitreous cavities of streptozotocin(STZ)reduced Wistar diabetic rats.METHODS:Adult male Wistar rats,9 weeks of age,were injected intraperitoneally with STZ to create diabetes models.Two weeks after the models were established,Ad.BDNF was administered into the vitreous cavities of rats.Four weeks after the models were established,the rats were killed and the retina was removed for Western blotting and Whole-mount immunohistochemistry for TH to observe the changes of TH and dopaminergic amacrine cells in retina.RESULTS:The protein levels of TH and the number of positive staining dopaminergic amacrine cells and the staining gray scale of experimental group without Ad.BDNF were statistically lower than that of the control group,there was statistical difference between two groups.But there were no statistical differences in experimental group with Ad.BDNF and control group.CONCLUSION:In the early stage of STZ diabetic,the administration of Ad.BDNF into the vitreous cavities can increase TH protein levels and the density of dopaminergic amacrine cells in the STZ rats’ retina.

中国辽宁省博士科研启动基金资助项目（No.20101145）