摘要
1背景眼外滤过手术一直是治疗青光眼的主要术式，而其术后滤过道瘢痕化是导致青光眼手术失败的主要原因。寻找有效和安全的抗瘢痕药物是抗青光眼滤过手术的研究热点。目的探讨羟基喜树碱（HCPT）在小梁切除术中的应用，评价HCPT对结膜下滤过泡的抗增生作用及其最佳剂量。方法12～16周龄健康新西兰大白兔40只制作抗青光眼滤过手术模型，采用随机数字表法将动物随机分为生理盐水组、丝裂霉素C（MMC）组、0．3g／LHCPT组及1．0g／LHCPT组，每组10只，均取右眼行常规小梁切除术，术中在不同组兔眼巩膜表面及巩膜瓣下分别放置含生理盐水、0．3g／LMMC、0．3g／LHCPT及1．0g／LHCPT的棉片5min。于术后l、4、7、14、21、28d用Icare眼压计测量眼压；裂隙灯显微镜下观察术眼滤过泡情况以评价各种药物的疗效，球结膜、角膜、前房炎症反应、虹膜周边切口及晶状体混浊情况，加前置镜后观察视网膜情况，以评估药物不良反应。于术后7、14、28d分别处死3、3、4只动物，取术眼5mm×5mm手术区组织，包括球结膜、结膜下组织及巩膜，分别行苏木精-伊红染色及Masson三重染色，比较各种药物的抗纤维组织增生效果。采用Kaplan—Meier分析比较各组兔术眼功能性滤过泡的生存时间。结果各组伺实验兔术眼的眼压随着时间的变化明显不同，差异均有统计学意义（F分组=20．79，P=0．00；F时间=85．34，P=0．00；F交互作用=2．13，P=0．01），其中MMC组和1．0g／LHCPT组术眼术后各时间点的眼压值均明显低于术前，差异均有统计学意义（P〈0．05），生理盐水组和0．3g／LHCPT组仅能分别维持低眼压至术后第7天和第14天。术后生理盐水组、MMC组、0．3g／LHCPT组及1．0g／LHCPT组术眼滤过泡存活时间分别为（11．3±2．8）、（19．5±2．4）、（13．3±2．2）和（20．2±4．5）d，差异有统计学意义（log rank=11．92，P〈0．01），1．0g／LHCPT组术眼滤过泡存活时间较其他组明显延长。术后7d内，各组术眼滤过泡面积和高度分级的差异均无统计学意义（P〉0．05），而术后7、14、28d，生理盐水组和0．3g／LHCPT组较1．0g／LHCPT组与MMC组的滤过泡面积明显减小，差异均有统计学意义（P〈0．05）。苏木精-伊红染色和Masson染色表明，MMC组与1．0g／LHCPT组术区组织中炎性细胞明：显减少，结膜下组织中纤维细胞增生量下降，胶原纤维染色减少。结论小梁切除术中局部应用1．0g／LHCPT能抑制术区组织的炎症反应和胶原纤维的增生，有效降低眼压，且功能性滤过泡维持时间长。【
Background The filtration surgery is the main method of treating glaucoma,which usually fails Clue to postoperative scarring. The study about application of anti-scarring agents in filtration surgery is a hotspot. Objective This study was to investigate whether topical administration of hydroxycamptotheein （HCPT） could be utsed to prevent postoperative scarring in after experimental glaucoma filtration surgery,and explore its optimal dose. Methods Trabeculectomy was performed on the right eyes of 40 New Zealand white rabbits to establish the trabeculectomy animal models, The rabbits were then randomized into normal saline solution group, 0.3 g/L mitomycin C（MMC） group,0.3 g/L HCPT group and 1.0 g/L HCPT group based on the intraoperative topical drugs using randomized number table method. The different drugs above-mentioned were put beneath the conjunctival flap and scleral flap for 5 minutes during the surgery. The intraocular pressure （IOP） was measured before and day 1,4, 7,14,21 and 28 after the surgery with Icare tonometer,and the filtering area and height were measured under the slit lamp microscope to assess the efficacy of various drugs. The adverse effects were evaluated by examining the responses of the ocular anterior segment and retinal change. The specimens at operative zone were obtained in 7,14 and 28 days after surgery with the size 5 mm^5 mm for the hematoxylin-eosin staining and Masson trichrome staining to estimate the anti-fibrosis effect of various drugs,and to evaluate the survival time of functional bleb. Kaplan-Meier analysis was used to compare the survival time of functional bleb of different groups. The use and care of the animals complied with the Regulation for the Administration of Affair Concerning Experimental Animals by State Science and Technology Committee. Results The IOP was significantly different in the rabbits from different groups among various time points （Fgroup =20. 79,P=0. 00; Ftime=85.34,P=0. 00; Finteraetion =2. 13,P=0. 01 ）. From 1 day through 28 days after operation,the IOPs in MMC group and 1.0 g/L HCPT group were significantly lower than those before operation （ all at P〈0.05 ）. The survival time of functional bleb of different groups was （ 11.3 ±2.8 ）, （ 19.5 ±2.4 ）, （ 13.3± 2.2） and （ 20.2 ± 4.5 ） days, respectively, showing a significant difference （ log rank = 11.92, P 〈 0. 01 ）, with a considerable prolong in the 1.0 g/L HCPT group. No significant change was found in the bleb area and height among the four groups within 7 days after operation,but postoperative 7,14,28 days,the area and height values of bleb were significantly smaller in the normal saline solution group and 0. 3 g/L HCPT group compared with the MMC group and 1.0 g/L HCPT group （all at P〈 0. 05 ）. Histopathological examination showed loosen subconjunctival tissue, less inflammatory cells and weaker collagenous fibrillary staining in the MMC group and 1.0 g/L HCPT group in comparison with the normal saline solution group and 0.3 g/L HCPT group. Conclusions The topical administration of 1.0 g/L HCPT inhibit the inflammatory response and collagen fibrosis and therefore prolong the survival time of functional bleb after glaucomatous filtering surgery.
出处
《中华实验眼科杂志》
CAS
CSCD
北大核心
2014年第2期131-136,共6页
Chinese Journal Of Experimental Ophthalmology
基金
国家自然科学基金资助项目（81271001）
