地塞米松和维甲酸缓释系统预防增生性玻璃体视网膜病变的实验研究

Study of antiproliferative effect of drug delivery system of dexamethasone and retinoic acid

目的研究地塞米松缓释系统(DexDDS)和维甲酸缓释系统(RADDS)预防增生性玻璃体视网膜病变(PVR)的效果和安全性。方法60只兔随机分为7组,A^E组建立PVR模型,A、B组为对照组,C、D、E组分别植入DexDDS、RADDS、DexDDS+RADDS,观察术眼前后段变化;F、G组植入DexDDS或RADDS,观察药物的毒性作用;检测各组玻璃体中Dex和RA的质量浓度变化。结果A、B组术眼术后前后段反应重,E组反应最轻,C、D组为中度反应。F、G组未见毒性作用;DexDDS在植入后1周即达到较高质量浓度并持续到6周,而RADDS在植入后6周质量浓度达到高峰并持续到8周。结论DexDDS和RADDS玻璃体腔内植入安全,联合应用可以有效地抑制PVR。

Objective To investigate the antiproliferative effect, safety and release of dexamethasone drug delivery system （DexDDS） and retinoic acid drug delivery system （RADDS） in an experimental animal model. Methods Vitrectomy was performed in 60 New Zealand albino rabbits, and the models of proliferative vitreoretinopathy （PVR） were created by the intravitrouse injection of 0. 2 ml of fibroblasts suspension in the animals of A, B, C,D, E group,and fibroblast was not used in F and G group. DexDDS, RADDS was implanted into vitreous cavity respectively in the right eyes of rabbits of C,D group and F,G group. DexDDS ＋ RADDS was administered into E group,blank DDS was implanted in B group and DDS was not used in A group. The anterior and posterior segments reactions after surgery were observed clinically. The toxicity reaction of retina, liver and kidney to DexDDS or RADDS was detected using flash ERG and light microscope respectively,and the concentration of the dexamethasone and retinoic acid were measured by HPLC. Results In PVR models, the changes of anterior and posterior segments of eyes were severer in A,B groups than in E group,and showed a middle degree of reaction in C group and D group. The mean intraocular pressure and ERG were no significant differences between pre-and post-operation in F and D groups. The high concentration of dexamethasone could be obtained in the 1 st week and maintained up to the 6th week,and the concentration of retinoic acid reached peak in the 6th week postoperatively up to the 8th week. Conclusion DexDDS and RADDS are safe to ocular tissue after intravitreous injection and they can release drug in a stable rate. DexDDS can inhibit the ocular inflammation postoperatively,and RADDS can prolong the development of PVR. Combination of both DDS can inhibit PVR formation effectively.