结膜下注射环孢霉素A微粒体的药物反应性

Experimental studies on drug reaction of cyclosporine A-containing microspheres after subconjunctival injection

目的 探讨环孢霉素 A微粒体结膜下注射的药物反应性。方法 健康新西兰白兔 6只 ,左眼为实验组 ,右眼为对照组。实验组球结膜下注射 15 g· L- 1的 Cs A微粒体 ,对照组球结膜下注射相同浓度的 Cs A溶液 ,每次 0 .2 m L,每 5 d1次 ,维持 30 d。用药结束后分别于 1、2、3月时各取 2只白兔处死 ,剪取注射部位的结膜及巩膜 ,立即用 AF固定液固定48h,然后脱水、包埋、切片和 HE染色。光学显微镜下观察注射部位的结膜和巩膜有无炎症细胞浸润、纤维包裹和坏死等情况。结果 注射 Cs A溶液后兔眼结膜水肿非常严重 ,注射 1次后 ,充血水肿需 3d才会消退 ;而实验组结膜充血水肿 2 d即消退。 Cs A微粒体组切片显示用药结束后第 1月仅结膜有少的炎症反应 ,第 2月后结膜已恢复正常 ;Cs A溶液组用药后第 1月炎症反应较显著 ,巩膜也有较少的炎症反应。第 3月时可观察到结膜和巩膜有纤维化形成。结论 Cs A微粒体的生物相容性较好 ,药物刺激性较小 。

Objective To evaluate the drug reaction of subconjunctival cyclosporine A-containing microspheres. Methods Six New Zealand white rabbits were studied. Their right eyes were classify in control group and left eyes were classify in trial group. Right eyes received subconjunctival injection with 0.2 mL of 1.5g·L -1 cyclosporine A-containing microspheres, left eyes received subconjunctival injection with same dosage and concentration of cyclosporine solutions, and a single subconjunctival injection was underwent every five days, and for 30 days. Two rabbits were killed at 1,2,3 months after undergoing subconjunctival injection, and rabbits' conjunctiva and sclera in the position of subconjunctival were cut out and immediately fixed using AF fixation solutions for 48 hours, then was desiccated,embed,sliced up and stained using HE. Pathological sections were observed to look for inflammatory cell infiltration, fiberized packs, and necrosis with light microscope. Results Conjunctival edema of rabbits' eyes which received subconjunctival injection with cyclosporine solutions was very serious. And fadeaway of conjunctival edema need 3 days after a single subconjunctival injection. But conjunctival edema lasted only 2 days in trial group. Only conjunctiva had minor inflammatory reaction at one month after the sixth subconjunctival injection finished in trial group; Inflammatory reaction of conjunctiva was very serious, and sclera also had minor inflammatory reaction at one month after medication finished in control group. And fibrosis of conjunctiva and sclera could be observed at three months.Conclusion Biocompatibility of cyclosporine A-containing microspheres is good. And its stimulation is lighter. Cyclosporine A-containing microspheres is promising to be developed as a long-acting cyclosporin A formulation.