环孢素A缓释系统眼内植入治疗葡萄膜炎的实验研究

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目的探讨环孢素A缓释系统(CsA DDS)玻璃体腔植入治疗实验性葡萄膜炎的有效性和安全性。方法43只新西兰白兔中,其中30只建立葡萄膜炎动物模型,按照随机数字表法分为4组,即空白对照组(A)6只、空白DDS植入组(B)6只、CsA口服治疗组(C)6只及CsA DDS植入组(D)12只,于术后不同时间点观察各组兔眼前房闪辉、房水细胞、前房渗出、玻璃体细胞以及玻璃体混浊度并进行分级,并进行视网膜电图(ERG)、眼和肝、肾组织病理学检查;余13只新西兰兔右眼植入CsA DDS,检测玻璃体腔CsA药物浓度。结果(1)30只实验兔均成功诱发葡萄膜炎模型。各时间点A、B、C组各项炎性指标分级均高于D组,A、B组间及C、D组间差异无统计学意义(P>0.05),D组与A、B组间差异有统计学意义(P<0.05);ERG检查显示A、B两组b波波幅降低幅度均较D组明显,差异有统计学意义(P<0.05);A、B组睫状体和视网膜有大量炎性细胞浸润,组织明显破坏,而C、D组则未见炎性细胞浸润,组织结构基本完整。(2)CsA DDS植入术后玻璃体腔药物浓度在1个月时达到(491.0±481.6)ng/ml,2个月时为(575.2±373.2)ng/ml,3个月时缓慢下降至(301.5±128.5)ng/ml。光镜检查未见眼内毒性反应。结论CsA DDS玻璃体腔植入能够在眼内维持安全有效的药物浓度,明显减轻兔眼葡萄膜炎性反应,为葡萄膜炎的治疗提供了一种新的用药途径。 Objective To investigate the efficacy and safety of cyclosporin A sustained-release system (CsA DDS) implantation in vitreous cavity in the treatment of experimental uveitis. Methods Thirty-three New Zealand white rabbits were divided into four groups according to the random number table: control group (A), blank control group (B), blank control group (CsA) (C) 6 and CsA DDS 12 (D). The anterior chamber glare, aqueous humor, anterior chamber exudation, vitreous cells and vitreous haze of rabbits in each group were observed at different time points after operation. And graded. Electroretinography (ERG), ocular, liver and kidney histopathological examination were performed. The other 13 New Zealand rabbits were implanted with CsA DDS in the right eye to detect the concentration of CsA in the vitreous. Results (1) 30 rabbits were successfully induced uveitis model. The indexes of inflammation in groups A, B and C were higher than those in group D at each time point, there was no significant difference between groups A and B and between groups C and D (P> 0.05) (P <0.05). The ERG examination showed that the decrease amplitude of b wave amplitude in group A and group B was significantly higher than that in group D (P <0.05) The retina has a large number of inflammatory cell infiltration, tissue was significantly damaged, while C, D group did not see the inflammatory cell infiltration, the basic integrity of the organizational structure. (2) The intravitreal drug concentration in CsA DDS group reached (491.0 ± 481.6) ng / ml at 1 month and (575.2 ± 373.2) ng / ml at 2 months and slowly decreased to 301.5 ± 128.5) ng / ml. Light microscopic examination showed no intraocular toxicity. Conclusion Intravitreal CsA DDS implantation can maintain a safe and effective drug concentration in the eye and significantly reduce the uveitis in rabbit eyes, providing a new route of treatment for the treatment of uveitis.
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