玻璃体腔注射塞来昔布一聚乳酸羟基醋酸共聚物缓释微球的安全性研究  

The effects of celecoxib-poly lactide-co-glycolide microparticles on rat retina after intravitreai injection

作　　者：陈鹏飞[1] 郝玉华[1] 安建斌[1] 崔月先[1] 马景学[1] 

机构地区：[1]河北医科大学第二医院眼科,石家庄050000

出　　处：《中华眼底病杂志》2013年第6期605-609,共5页Chinese Journal of Ocular Fundus Diseases

基　　金：基金项目：河北省医学科学研究重点课题计划（20i20069）

摘　　要：目的观察玻璃体腔注射塞来昔布一聚乳酸羟基醋酸共聚物缓释微球（CEL—PLGA—MS）对视网膜的安全性。方法32只雄性BrownNorway大鼠随机分为CEL—PLGA—MS组和塞来昔布（celecoxib）组，每组各16只。CEL—PLGAMS组分为4个剂量组，每组各4只。分别玻璃体腔注入含celecoxib40、80、160、320p．mol／L的聚酸乳羟基醛酸共聚物（PLGA）微球。Celecoxib组分为4个剂量组，每组各4只。分别玻璃体腔注入celecoxib40、80、160、320／~mol／L；磷酸盐缓冲液（PBS）对照组4只，2只双眼玻璃体腔注入0．01mol／LPBS溶液，正常对照组2只，双眼不处理。光相干断层扫描（0CT）测量各组视网膜厚度，光学显微镜观察各组视网膜微结构变化，透射电子显微镜观察各组视网膜细胞的超微结构变化。结果OCT检查结果显示，正常对照组和PBS对照组视网膜厚度比较，差异无统计学意义（F=0．12，P〉0．05）。注药后1周，CEL-PLGAMS、celecoxib各组视网膜厚度均大于正常对照组、PBS对照组。组问视网膜厚度比较，差异有统计学意义（F=9．62、46．13；P〈0．01）。CEL—PLGA-MS各组视网膜厚度小于celecoxib各组。组间视网膜厚度比较，差异有统计学意义（F=165．15，P〈0．01）。CEL—PLGA—MS40、80、320μmol／L组视网膜厚度大致相同。组间视网膜厚度比较，差异有统计学意义（F=4．79，P〈0．01）。Celecoxib160、320μmol／L组视网膜厚度大于celecoxib40、80umol／I。组。组间视网膜厚度比较，差异有统计学意义（F=28．10，P％0．01）。注药后2周，CEL—PLGA—Ms各组视网膜厚度与eelecoxib各组比较，差异无统计学意义（F=3．79，P〉0．05）。且较注药后1周时视网膜厚度逐渐减小，差异有统计学意义（F=7．28、103．99；P〈0．01）。注药后4周，CEL—PLGA—MS各组视网膜厚度小于celecoxib各组。组间视网膜厚度比较，差异有统计学意义（F=19Objective To investigate the effects of （CEL-PLGA MS） on rat retina after intravitreal injection. celecoxib-poly lactide-co-glycolide microparticles Methods A total of 32 male Brown Norway rats were randomly divided into CEL-PLGA-MS group and celecoxib group, 16 rats in each group. The rats in CEL-PLGA-MS group were divided into four dosage group, four rats in each group, which received intravitreal injection of PLGA with celecoxib at the concentration of 40, 80, 160, 320μmol/L, respectively. The rats in celecoxib group were divided into four dosage group, four rats in each group, which receivedintravitreal injection of celecoxib at the concentration of 40, 80, 160, 320 μmol/L, respectively. Phosphate buffer solution （PBS） was injected in two rats as PBS control group. Two rats as normal control group received no treatment. The difference of retinal thickness among groups was measured by optical coherence tomography （OCT）. The morphological and histological change of retina was evaluated under light microscope and transmission electron microscope. Results There was no difference of retinal thickness between normal control group and PBS control group （F = 0.12, P~〉 0.05）. At the first week after injection, the retinal thickness of CEL-PLGA-MS group and celecoxib group were thicker than that in normal control group and PBS control group （F = 9.62, 46.13; P〈 0.01）. The retinal thickness of celecoxib group was thicker than that in CEL-PLGA-MS group （F = 165.15, P〈 0.01）. The retinal thickness was estimated equal among 40, 80, 320 μmol/L dosage groups in CEL-PLGA MS group （F= 4.79, P^0.01）. The retinal thickness of 160, 320 μmol/L dosage group were thicker than that in 40, 80 μmol/L dosage group in celecoxib group （F=28.10, P〉0.01）. At the second week after injection, there was no difference of retinal thickness between CEL-PLGA-MS and celecoxib group （F= 3.79, P〈0. 05） ; the retinal thickness of CEL-PLGA-MS and celecoxib group became thinner gradually compare to the

关 键 词：环氧化酶2抑制剂 毒性 环氧化酶2抑制剂 治疗应用 迟效制剂 毒性 脉络膜新 生血管化 药物疗法 

分 类 号：R774[医药卫生—眼科]