兔眼玻璃体腔注射更昔洛韦的视网膜毒性研究  

Retinal toxicity study of intravitreal ganciclovir in albino rabbit

作　　者：狄宇 郭立斌 叶俊杰[1] 徐海燕[1] Di Yu;Guo Libin;Ye Junjie;Xu Haiyan(Department of Ophthalmology,Peking Union Medical Academy of Medical Sciences,Beijing 100730,China;Department of Ophthalmology,Beijing Tsinghua Changgung Hospital,Beijing 102218,China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院眼科,100730 [2]北京清华长庚医院眼科,102218

出　　处：《中华眼科杂志》2020年第4期279-285,共7页Chinese Journal of Ophthalmology

摘　　要：目的探讨不同剂量更昔洛韦注射于健康兔眼玻璃体腔后的视网膜毒性反应。方法实验研究。新西兰无色素雄兔24只(48只眼),随机数字表法分为4个组,每组12只眼。3个实验组玻璃体腔均注射药液5 ml,分别含更昔洛韦400μg、2 mg及5 mg,对照组玻璃体腔注射等量生理盐水。兔眼玻璃体腔注药前、后1、2、4周行全视野视网膜电图检测,另外于注药后1、2、4周每组摘除2只兔双眼行光镜和透射电镜观察。所有数据采用多个独立样本非参数检验方法进行统计学比较。结果全视野ERG Max-R a波振幅于注药后1周组间差异有统计学意义(χ2=8.319,P=0.04),两两比较5 mg组(140.50μV)较对照组(165.00μV)均明显下降(χ2=-2.830,P=0.028)。Max-R b波振幅于注药后4周组间差异有统计学意义(χ2=-10.626,P=0.014),5 mg组(261.50μV)较对照组(398.00μV)均明显下降(χ2=-2.973,P=0.018)。30 Hz闪烁反应b波振幅于注药后1、2、4周组间差异有统计学意义(χ2=17.589,8.225,8.997;P=0.001,0.042,0.029),两两比较5 mg组(71.30、106.00、63.60μV)较对照组(118.50、129.00、116.50μV)明显下降(χ2=-4.142,-2.826,-2.713;P=0.000,0.028,0.040)。光镜下观察2 mg组注药后4周、5 mg组注药后2、4周视网膜组织形态出现内核层细胞排列较疏松,神经节细胞核周间隙增宽,外丛状层染色较淡等异常改变。透射电镜下观察注药后4周各实验组视网膜超微结构可见光感受器外节膜盘疏松排列紊乱,内节部分线粒体肿胀和积水变等异常改变,且依次加重。结论健康兔眼玻璃体腔注射更昔洛韦400μg未见视网膜功能及组织形态异常,注射2 mg和5 mg后可见一定视网膜毒性反应,5 mg更显著。提示临床应用更昔洛韦治疗急性视网膜坏死时应选择有效的最小剂量,最大限度避免视网膜毒性反应的发生。Objective To elevated the retinal toxicity of intravitreal ganciclovir in albino rabbit eyes.Methods Experimental study.Twenty-four New Zealand albino rabbits(forty-eight eyes)were divided into four groups by random.Three groups were prepared for ganciclovir experiment,named A,B,C.Each group received intravitreal injection ganciclovir dose at 400μg/0.05 ml,2 mg/0.05 ml and 5 mg/0.05 ml respectively.The other group named D served as a control accepted intravitreal injection 0.9%normal saline 0.1 ml.Before and after 1,2 and 4 weeks,flicker full field electroretina gram(ERG)was recorded.After 1,2 and 4 weeks light and electron microscopic tests were recorded for further toxicity study.Results There was significant difference in amplitude of maximal combined response a wave in one week(χ2=8.319,P=0.04),and pairwise comparison the 5 mg group(140.50μV)was significantly lower than the control group(165.00μV)(χ2=-2.830,P=0.028).Maximal combined response b wave in four weeks(χ2=-10.626,P=0.014),and pairwise comparison the 5 mg group(261.50μV)was significantly lower than the control group(398.00μV)(χ2=-2.973,P=0.018).30 Hz flicker response in one,two and four weeks(χ2=17.589,8.225,8.997,P=0.001,0.042,0.02),and pairwise comparison the 5 mg group(71.3μV,106.00μV,63.60μV)was significantly lower than the control group(118.50μV,129.00μV,116.50μV)(χ2=-4.142,-2.826,-2.713,P=0.000,0.028,0.040).There was no histologic retinal toxicity evidence of group 400μg and control group observed by light microscopy in any stage of the study.Histologic changes of group 2 mg four week later,group 5 mg two and four week later include inner nuclear layer loose arranged,nuclear of ganglia were widened and outer plexiform layer stained less in four week later.By electron microscopic observation,the ultrastructure of retina changed to different degrees and became worse in each experimental group with significant mitochondrial swelling and hydropic changes were seen in the inner segments of photoreceptors,loosely arranged and disord

关 键 词：视网膜坏死综合征 急性 更昔洛韦 玻璃体内注射 药物毒性 

分 类 号：R77[医药卫生—眼科] R9[医药卫生—临床医学]