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环孢素A药物递送系统眼内植入治疗实验性葡萄膜炎

[Intraocular implantation of cyclosporine A drug delivery system in the treatment of experimental uveitis].

作者信息

Dong Xiao-guang, Xu Yu-mei, Yuan Gong-qiang, Shi Wei-yun, Xie Li-xin, Wang Shen-guo

机构信息

Shandong Eye Institute, Qingdao 266071, China.

出版信息

Zhonghua Yan Ke Za Zhi. 2005 Jul;41(7):636-41.

Abstract

OBJECTIVE

To investigate the effects and safety of cyclosporine A drug delivery system (CsA DDS) implanted into vitreous cavity on the treatment of experimental rabbit uveitis.

METHOD

A model of uveitis was established in 30 New Zealand white rabbits (30 eyes). The rabbits were randomized into control group (group A, 6 eyes), intravitreal non-medicated DDS group (group B, 6 eyes), oral CsA group (group C, 6 eyes) and intravitreal CsA DDS group (group D, 12 eyes). The inflammatory parameters such as floating cells, flaring and exudation in anterior chamber were graded. The cells infiltration and degree of opacity in vitreous were scored as well. The electroretinography and histopathological examination in eye, liver and kidney were recorded. In addition, CsA level in vitreous cavity was measured by HPLC in another 13 New Zealand white rabbits that received intravitreal implantation of CsA DDS.

RESULTS

Uveitis was successfully induced in the 30 eyes. The inflammation in groups A, B and C was more severe than group D. There was no significant difference between groups D and A or B (P < 0.05). The electroretinography showed more significant b-wave depression in groups A and B than group D (P < 0.05). A large amount of inflammatory cells infiltration and marked tissue disorganization were found at ciliary body and retina in groups A and B. The mean drug level in vitreous cavity ws (491.0 +/- 481.6) ng/ml at 4 weeks, (575.2 +/-0373.2) ng/ml at 8 weeks and (301.5 +/- 128.5) ng/ml at 12 weeks. No toxicity could be detected in histological examination by light microscopy.

CONCLUSION

Sustained therapeutic drug level could be achieved by implanting CsA DDS into vitreous cavity. It may effectively reduce the ocular inflammation in the rabbit model of uveitis.

摘要

目的

探讨玻璃体腔内植入环孢素A药物递送系统(CsA DDS)治疗实验性兔葡萄膜炎的疗效及安全性。

方法

选取30只新西兰白兔(30只眼)建立葡萄膜炎模型。将兔子随机分为对照组(A组,6只眼)、玻璃体腔内非药物DDS组(B组,6只眼)、口服CsA组(C组,6只眼)和玻璃体腔内CsA DDS组(D组,12只眼)。对前房内的浮游细胞、闪光和渗出等炎症参数进行分级。对玻璃体中的细胞浸润和混浊程度也进行评分。记录眼、肝和肾的视网膜电图及组织病理学检查结果。此外,在另外13只接受玻璃体腔内植入CsA DDS的新西兰白兔中,用高效液相色谱法测量玻璃体腔内的CsA水平。

结果

30只眼成功诱导出葡萄膜炎。A、B和C组的炎症比D组更严重。D组与A组或B组之间无显著差异(P < 0.05)。视网膜电图显示,A组和B组的b波降低比D组更显著(P < 0.05)。A组和B组的睫状体和视网膜有大量炎性细胞浸润和明显的组织紊乱。玻璃体腔内的平均药物水平在4周时为(491.0±481.6)ng/ml,8周时为(575.2±373.2)ng/ml,12周时为(301.5±128.5)ng/ml。光学显微镜组织学检查未发现毒性。

结论

玻璃体腔内植入CsA DDS可实现持续的治疗药物水平。它可能有效减轻兔葡萄膜炎模型的眼部炎症。

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