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目的 了解非甾体类抗炎药物双氯酚酸钠 (diclofenac sodium,DFS)玻璃体内注射对视网膜的毒性作用 ,探索眼内应用 DFS的安全剂量范围。 方法 2 8只健康成年大耳白兔 ,随机分为 7组 ,分别于每组右眼玻璃体内注入 4、5、6、7、8、9、10 mg/ ml的 DFS溶液 0 .1ml,左眼为对照眼。注药前及注药后 1、3、7、14、2 1、2 8d分别行双眼视网膜电图 (electroretinogram,ERG)检查。注药后 10、2 8、30 d分别摘除眼球行光学显微镜和透射电镜检查。 结果 注药剂量 0 .4、0 .5 mg组 ERG明、暗适应 b波波幅比率与注药前相比差异无显著意义 ,透射电镜及光学显微镜检查均未见组织结构有明显异常。 0 .6 mg组在注药后 1dERG明适应 b波波幅比率较注药前明显下降 (P<0 .0 5 ) ,注药后 3d开始恢复 ,至注药后 14 d已达注药前水平 (P>0 .0 5 ) ,光学显微镜及透射电镜检查显示视网膜组织已出现水肿等可逆改变 ,部分仍维持正常结构。 0 .7~ 1.0 mg组 ERG b波波幅比率与注药前相比明显下降 (P<0 .0 5 ) ,且不能恢复 ,光学显微镜及透射电镜检查显示视网膜各层结构损伤 ,在注药后 10、30 d均可见到细胞核染色质浓缩集聚、细胞坏死等不可逆改变。 结论 DFS玻璃体内注射的最大安全剂量不得超过 0 .6 mg。当注药剂量大于或等于 0
Objective To investigate the toxic effects of intravitreal injection of diclofenac sodium (DFS), a nonsteroidal antiinflammatory drug, on the retina and to explore the safe dosage range of intraocular DFS. Methods Twenty eight healthy adult white rabbits were randomly divided into 7 groups. The left eye was injected with 0.1 ml DFS solution of 4, 5, 6, 7, 8, 9, and 10 mg / ml respectively Eye as a control eye. Bilateral electroretinogram (ERG) examination was performed before injection and at 1,3,7,14,2 and 1,28 days after injection. 10,28,30 d after injection were removed eyeball optical microscopy and transmission electron microscopy. Results There was no significant difference in the amplitude of ERG and ERB between the injection dose of 0.4, 0.5 and 5 mg groups before injection, and no significant abnormality of the tissue structure was observed by transmission electron microscopy and light microscopy. In the 0.6 mg group, the amplitude of the adaptive b wave amplitude on the 1st day after injection was significantly lower than that before injection (P <0.05), and recovered on the 3rd day after injection, reaching the pre-injection level 14 days after injection (P> 0.05). Optical microscope and transmission electron microscopy showed that edema and other reversible changes were observed in retinal tissue, and some still maintained normal structure. The amplitude of ER b b wave in the 0.7-7.0 mg group was significantly lower than that before injection (P <0.05), and could not be recovered. The structure of the retina was observed by optical microscope and transmission electron microscope. 10,30 d can be seen in the nuclear chromatin condensation, necrosis and other irreversible changes. Conclusion The maximum safe dose of intravitreal DFS injection should not exceed 0.6 mg. When the injection dose is greater than or equal to 0