透明质酸钠对兔含苯扎氯铵溴莫尼定眼表毒性保护作用的研究  

Protection effect of sodium hyaluronate on ocular surface toxicity induced by Benzalkonium chloride-preserved brimonidine in rabbits

作　　者：余芬芬[1] 刘杏[1] 钟毅敏[1] 毛真[1] 郭歆星[1] 李媚[1] 曹丹[1] 陈翔熙 

机构地区：[1]中山大学中山眼科中心眼科学国家重点实验室,广州510060

出　　处：《中华眼科杂志》2013年第11期973-980,共8页Chinese Journal of Ophthalmology

基　　金：广东省自然科学基金（S2011010006046）;眼科学国家重点实验室创新基金（2010C03）

摘　　要：目的 探讨透明质酸钠（SH）对含防腐剂苯扎氯胺（BAK）的酒石酸溴莫尼定滴眼液所致兔眼表毒性的影响.方法 实验研究.将30只新西兰大白兔按随机数字表法分为3组（每组10只）：无干预对照组;0.2％酒石酸溴莫尼定联合磷酸盐缓冲溶液（PBS）滴眼组（PBS处理组）;0.2％酒石酸溴莫尼定联合0.3％ SH滴眼组（SH处理组）,连续用药60d.于第0、31、61天行基础泪液分泌测量、角膜荧光素染色评分、角结膜虎红染色评分、结膜印迹细胞检查;于第61天取材行结膜上皮细胞原位凋亡检测（TUNEL法）,结膜组织苏木素-伊红染色炎症细胞计数,角膜组织扫描电镜、角膜及球结膜组织透射电镜观察超微结构变化.荧光素及虎红染色评分比较采用Kruskal-Wallis多组秩和检验法;基础泪液分泌量、结膜杯状细胞数量及结膜炎症细胞浸润数量比较采用重复测量方差分析法.结果 第61天各组荧光素及虎红染色评分差异有统计学意义（H=22.031,15.303;P＜0.01）,PBS处理组荧光素及虎红染色评分[（1.5,1～2）,（1,1～2）]较正常对照组[（0,0～1）,（0,0～1）]高（均P＜0.001）,SH处理组荧光素及虎红染色评分[（0,0～1）,（1,0～1）]较PBS处理组低（均P＜0.01）.第61天各组基础泪液分泌量及杯状细胞密度差异有统计学意义（F=7.980,14.545,P＜0.01）：PBS处理组的基础泪液分泌量及杯状细胞密度[（6.61±0.38） mm,（68.06±3.61）个/HP]较对照组[（9.43±0.57）mm,（87.73±2.34）个/HP]减少（P＜0.01）;而SH处理组[（8.75±0.57）mm,（82.31 ±1.64）个/HP]较PBS处理组多（P＜0.05,＜0.01）.第61天各组球结膜炎症细胞数差异有统计学意义（F=56.306,P＜0.01）,PBS处理组[（73.18±2.17）个/HP]和SH处理组[（48.79±2.64）个/HP]炎症细胞数均较对照组[（39.89±2.03）个/HP]多（P＜0.01）;但SH处理组较PBS处理组炎症细胞数少（P ＜0.001）.第61天SH处理组较PBS处�Objective To investigate the protective effects of sodium hyaluronate on ocular surface toxicity induced by a prolonged use of benzalkonium chloride-preserved Brimonidine eye drops.Methods Experimental study.Thirty adult female New Zealand rabbits were divided into three groups with randomized numbers design.Ten rabbits were treated with 0.2％ Brimonidine eye drops and PBS （PBS group）,the other ten rabbits with 0.2％ Brimonidine combined with sodium hyaluronate eye drops （SH group）,and control group received no treatment for 60 days.Schirmer test,fluorescein （FL） and Rose Bengal （RB） staining,conjunctival impression cytology specimens collecting were performed on day 0,31,and 61.Apoptosis of conjunctival epithelium was detected by in situ terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay on day 61.Conjunctival inflammation was observed by hematoxylin eosin staining.Histomorphological changes of cornea and conjunctiva were observed by light microscopy,and scanning and transmission electron microscopy at day 61.Fluorescein and Rose Bengal scores were analysed by Kruskal-Wallis test.Schirmer scores,goblet cell density and inflammatory cells infiltration were analysed by repeated measures analysis of variance.Results There were significant differences in fluorescein and Rose bengal （H =22.031,15.303,P ＜ 0.01） staining among the groups on day 61.Compared with the control group （FL：0,0-1,RB：0,0-1）,fluorescein and Rose Bengal scores were significantly （P ＜ 0.001） increased in PBS group （FL：1.5,1-2,RB：1,1-2）,whereas was significantly （P ＜ 0.001） decreased in SH group （FL：0,0-1 RB：1,0-1） when compared to PBS group.There were significant differences in aqueous tear production and goblet cell density （F =7.980,14.545,both P ＜ 0.01） among the groups on day 61.Compared with the control group [（9.43 ± 0.57） mm,（87.73 ± 2.34/HP）],Schirmer scores and goblet cell density were significantly （P ＜ 0.01） reduced in PBS-treat

关 键 词：透明质酸 喹恶啉类 苯扎胺化合物 眼药水 

分 类 号：R965[医药卫生—药理学]