兔眼玻璃体腔注射国产曲安奈德的视网膜毒性研究

Study of toxicity of intravitreous injection with domestic triamcinolone acetonide on rabbits retina

目的:研究常规剂量国产曲安奈德(Triamcinolone Acetonide,TA)玻璃体腔内注射对兔视网帧的毒性作用。方法:纯种健康新西兰大白兔48只行玻璃体腔内注射,随机选取24只兔子右眼注射生理盐水0.1ml作为对照A组,该24只兔子左眼注射TA混悬液4mg/0.1ml作为试验B组,其余24只兔子右眼注射去赋形剂的TA0.1ml(去除的赋形剂用生理盐水补足)作为试验C组,其左眼注射从曲安佘德混悬液中分离的赋形剂0.1ml作为试验D组。每只动物于注药前及注药后3天、2周及1月各时间点行双眼FERG检查,检查后处死动物,取出眼球行视网膜光学及电子显微镜检查,观察其结构的改变。结果:各实验组兔眼注药前后FERG b波潜伏期无明显变化,在注药后短时间内有b波振幅的降低,差异具有统计学意义(P<0.001);赋形剂组在注药后1月还有b波振幅的降低,差异具有统计学意义(P<0.001)光学及电子显微镜观察,赋形剂组在注药后各时间点均有视网膜结构的改变,去赋形剂组以及TA混悬液组只在短时间内有视网膜结构的改变。结论:4mg国产TA兔眼玻璃体腔注射短期内可引起视网膜结构和功能的轻度改变,但这种改变只是暂时性和可逆的,其对视网膜的毒性作用可能主要是由赋形剂引起的。

Objective：To investigate the toxicity effect of intravitreous injection with conventional dosage of domestic triamcinolone acetonide （TA） on rabbits retina. Methods：Forty-eight healthy purebred New Zealand white rabbits underwent intravitreous injection. The right eye of the 24 animals was injected with sterile saline solution 0.1ml as the control A group; and the left eye was injected with TA suspension 4mg （0.1ml） as the B experimental group;The right eye of the other 24 animals was injected with TA 0.1ml without excipient as the C experimental group,the excipient removed was supplemented with terile saline solution;and the left eye was injected with excipient 0.1ml separated from TA suspension as the D experimental group. Flash electroretinography （FERG） was performed on each animal before intravitreous injection,3 days,2 weeks ,and 1 months after the injected. After the examination the animal was killed and the eyeballs were extirpated at the three points of time after the injected. The uhrastructural changes of the retina were observed by light and electron microscopy. Results：No significant difference was found in the latent period of b-wave of FERG before and after the injected,but the amplitudes of b-wave of FERG was lower in all the groups than that before the treatment in a short time after the injected （P 〈 0.001 ）.The amplitudes of b-wave of FERG was still lower in the excipient group 1 month after the injected （P 〈 0.001 ）. The results of light and electron microscopy showed the uhrastructural changes of the retina in the excipient group at all the three points of time after the injected, only short-time uhrastructural changes in the other groups. Conclusion：Intravitreous injection of domestic TA with the dosage of 4mg may make the uhrastructure changes and function of retina in short term,but the changes are temporal and reversible, and may mainly come from the excipient.