噻吗心安和溴莫尼定滴眼液对兔眼表组织的影响  

Effects of timolol and brimonidine eyedrops on rabbit ocular surface

作　　者：毛真[1] 刘杏[1] 钟毅敏[1] 王涛[2] 黄晶晶[1] 肖辉[1] 李媚[1] 

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 [2]中山大学附属第三医院眼科

出　　处：《中华生物医学工程杂志》2009年第5期344-348,共5页Chinese Journal of Biomedical Engineering

基　　金：广东省科技计划项目（2007A060305009）

摘　　要：目的探讨降眼压药物噻吗心安滴眼液和溴莫尼定滴眼液及各自的防腐剂硫柳汞和氯化苯甲烃胺（BAC）对兔眼表组织的影响。方法15只新西兰大白兔，随机分为对照组（3只）、噻吗心安组（T组，6只）和溴莫尼定组（B组，6只）。实验兔右眼使用噻吗心安或溴莫尼定滴眼液，左眼使用对应的防腐剂硫柳汞和BAC，每Et2次，连续用药30d。取球结膜组织进行HE染色并计数结膜上皮层炎性细胞数；角膜行扫描电镜检测并进行上皮损害分级评分。结果HE染色示对照组兔球结膜上皮细胞排列整齐，用药后各组结膜上皮细胞层数增多，排列较对照组紊乱。与对照组比较，噻吗心安滴眼液、溴莫尼定滴眼液、防腐剂硫柳汞和BAC均可导致球结膜上皮层炎性细胞浸润增多（55．8±6．9，71．0±8．8，56．o＋7．1，62．5＋7．1比32．3±8．8，均P〈O．05）。角膜扫描电镜示除对照组外其他各组角膜上皮细胞表面的微绒毛丢失、细胞空洞和暗细胞增加；各实验组角膜上皮损害评分均高于对照组（P〈0．05）。溴莫尼定滴眼液引起的损害较噻吗心安滴眼液明显（P〈0．05），但两种滴眼液和对应的防腐剂对左右两眼的损害差异无统计学意义（P〉0．05）。结论噻吗心安、溴莫尼定滴眼液及防腐剂硫柳汞和BAC使用1个月后可导致兔球结膜炎性细胞增加和角膜上皮细胞损伤；防腐剂是引起眼表损伤的主要原因。溴莫尼定滴眼液对兔眼表的损伤较噻吗心安滴眼液严重。Objective To investigate the effects of two eyedrops containing timolol, brimonidine and their preservatives （thiomersal in timolol, and benzalkonium chloride in brimonidine） respectively, in the histology of rabbit eye surface. Methods A randomized study was conducted in fifteen New Zealand white rabbits allocated three groups： control group （n=3） , the timolol group （group T, n=6） and the brimonidine group （group B, n=6）. The rabbits in groups B or T received eyedrop of timolol or brimonidine in the right eyes and their preservatives （thiomersal or benzalkonium chloride） in the left eyes, twice daily for 30 days. Corneal epithelial damage and grading was evaluated by scanning electron microscopy, and bulbar conjunctival specimens were examined by HE stain as well as counting conjunctival epithelial inflammatory ceils. Results Compared with the tidily arranged epithelial layers of conjunctiva in control group, the medicated rabbits showed increased layers and irregular arrangement of the cells. The lymphocyte count was 32.3±8.8 in the control group versus 55.8±6.9 in timolol, 71.0±8.8 in brimonidine, 56.0±7.1 in thiomersal and 62.5±7.1 in benzalkonium chloride （all P〈0.05）. Scanning electron microscopy revealed loss of microvillae, formation of celluar vacuolation and increased dark cells on the surface of corneal epithelium in all eyes except those in control group. Corneal epithelium damage scores were higher in experiment groups than in control group （P〈0.05）. Brimonidine produced significantly more damage than timolol （P〈0.05）, but such difference was not found between eyedrops and preservative agents （P〉0.05）. Conclusions When applied to rabbit eyes for one month, brimonidine, timolol and their preservatives result in corneal damage and conjunctival inflammatory cell infiltration. The preservatives may play a major role in the ocular surface adverse effects. Brimonidine appears to have more influences on ocular surface compared with timolol.

关 键 词：青光眼 角膜 结膜 防腐剂. 药物 药物毒性 

分 类 号：R775[医药卫生—眼科] R965.2[医药卫生—临床医学]