摘要
目的探讨两性霉素B缓释系统（AmB—DDS）玻璃体腔植入对烟曲霉菌性眼内炎的疗效、AmB-DDS的药物释放规律及最佳释药量。方法选取40只新西兰白兔作为实验动物。（1）Amb-DDS治疗烟曲霉菌性眼内炎疗效学观察：动物玻璃体腔内注入烟曲霉菌悬液，48h后随机分为5组，A组为空白对照组（6只眼），B组为空白DDS组（6只眼），C组为两性霉素B玻璃体腔内注射组（6只眼），D组为AmB—DDS250μg植入联合玻璃体切除术组（8只眼），E组为AmB—DDS500μg植入联合玻璃体切除术组（8只眼）。术后不同时间点检测前房闪辉、细胞及玻璃体混浊程度，取玻璃体腔内容物行涂片检查和真菌培养，2个月时取眼球标本行病理学检查；（2）AmB—DDS玻璃体腔内药物浓度检测：H组玻璃体切除术后植入500μg AmB—DDS1个（6只眼），术后第1、3、7天及2、4、6、8周取玻璃体液，高效液相色谱分析法检测药物浓度。结果A、B组全部发生严重眼内炎，伴眶内感染，组间比较差异无统计学意义（P〉0．05）；C、D、E组炎性反应较A、B组轻，差异有统计学意义（P≤0．005）；E组玻璃体混浊程度较C组轻，7～14d前房反应较C组轻，差异均有统计学意义（P≤0．005）；D组5只眼、E组8只眼治愈，差异有统计学意义（x^2=10．494，P=0．003）。不同时间点取玻璃体腔内容物涂片，所有标本6周内均见菌丝，真菌培养仅A、B组为阳性。病理学检查示治愈眼结构正常，感染未控制眼均萎缩，球壁结构被破坏。H组术后第1天即有释药，药物浓度迅速升高超出有效抑菌浓度，观察期内释药较平稳。结论AmB—DDS玻璃体腔内植入治疗烟曲霉菌性眼内炎安全有效，释药恒定，速率得当；以含药量为500μg的AmB—DDS治疗效果最佳。（中华腰科杂志，2007，43：546-553）
Objective To observe a new amphotericin B drug delivery system （AmB-DDS）, and investigate the therapeutic effects of AmB-DDS on an experimental Aspergillus fumigatus endophthalmitis. Methods （1） In order to observe the effects of AmB-DDS, thirty-four New Zealand albino rabbits were intravitreal injected Aspergillus fumigatus suspension （ 10^3 colony forming unit, CFU ） in applanation of vitreous body before therapy 48 hours. All models were randomly divided into five groups. Group A was the empty control group, treated nothing after Aspergillus fumigatus injection, group B was the empty DDS implantation combined with vitrectomy, no treatment after DDS implanted, group C： AmB 5 μg-injection combined with vitrectomy, the injection was repeated two week later, group D： 250 μg AmB-DDS intravitreal implantation combined with vitrectomy, Group E： 500 μg AmB-DDS intravitreal implantation combined with vitrectomy. Aqueous flare, cells, anterior vitreous cells and vitreous opacity were graded, and vitreous humor smear and culture were performed at different time points after operation in 8 weeks. Two months after operation, light microscopy was used histology evaluation. （2）To observe the release of AmB-DDS in Group H（6 eyes）, 500 μg AmB-DDS were implanted in the eye of the rabbits after vitrectomy,vitreous humor was aspirated and the concentrations of amphotericin B were determined by high performance liquid chromatography （HPLC）. Results The inflammation response was lower in groups C, D, E than groups A, B. There was no significant statistical difference between group A and group B（P 〉0.05）, but differences among C,D,E and groups A,B were significant（P≤0.005）. The inflammation grade was lower in group E than group C（P≤0. 005）. There was significant statistical difference between the cure effect of group E and group D （x^2 = 10. 494, P = 0. 003）. All of vitreous humor smears was positive in 1.5 months after surgery, but the culture was only positive in group A, and B. Pathological examination indicated that normal structure was disappeared in the eyes with Aspergillus endophthalmitis. At the first day after surgery, AmB were observed by analysis of HPLC, there was sustained AmB release in the group of AmB-DDS application during the observation periods. Conclusions The degradable AmB-DDS can effectively suppress the inflammation of the rabbit model of Aspergillusfumigatus endophthalmitis. As an alternative to the current routine therapy, it can be used for the treatment of Aspergillusfumigatus endophthalmitis. （Chin J Ophthalmol, 2007,43：546- 553）
出处
《中华眼科杂志》
CAS
CSCD
北大核心
2007年第6期546-553,共8页
Chinese Journal of Ophthalmology
基金
国家高技术研究发展计划（863计划）（2002AA223136）
山东省科技厅发展计划重大项目资助（021100105）
青岛市科技局院士科研项目（02KGYSH-01）
关键词
两性霉素B
药物释放系统
曲霉菌
烟
眼内炎
眼感染
真菌性
Amphotericin B
Drug delivery systems
Aspergillus fumigatus
Endophthalmitis
Eye infections, fungal
