张靖，姜华，陈昆山，李海波，蒋贻洲，林雀卿，李丹，黄晓明，肖湘生

·实验研究Experimental research·

经眼动脉灌注治疗兔成视网膜细胞瘤

张靖，姜华，陈昆山，李海波，蒋贻洲，林雀卿，李丹，黄晓明，肖湘生

目的评估兔成视网膜细胞瘤（retinoblastoma，RB）模型的建立及经导管眼动脉灌注（selective ophthalmic arterial injection，SOAI）治疗兔RB的可行性。方法HXO-Rb44RB细胞予中心细胞室培养，取对数生长期HXO-Rb44细胞，用PBS配成浓度为2.0×107个/ml的细胞悬液，抽取0.1 ml细胞悬液注射于6只SPF级新西兰兔右眼视网膜间隙下。接种肿瘤细胞前3 d和注射后1个月臀部注射环孢素A 15 mg·kg-1·d-1，1个月后减量至10 mg·kg-1·d-1并持续到实验结束。将RB兔分为对照组3只和实验组3只，对照组灌注0.9%氯化钠溶液15 ml，实验组将美法仑2.5 mg用0.9%氯化钠溶液稀释至15 ml后灌注。术后分别于7、14 d比较两组肿瘤生长情况。结果注射环孢素A期间，实验兔不良反应轻微，6只均建模成功。7次插管中6次成功插至眼动脉。SOAI术后1周，实验组肿瘤可见明显缩小，2周后均消失。SOAI术后，实验组仅1只见右眼轻度红肿、流泪，1周后红肿自行消退。结论SOAI治疗RB兔具有可行性，为进一步经眼动脉灌注治疗RB的基础研究提供了参考。

成视网膜细胞瘤；动物模型；经眼动脉灌注术；美法仑

【Abstract】ObjectiveTo investigate the establishment of retinoblastoma model in experimental rabbits，and to evaluate the feasibility and success rate of selective ophthalmic arterial perfusion of melphalan in treating retinoblastoma in experimental rabbits.MethodsThe human retinoblastoma HXO-Rb-44 cell line was cultured in the cell culture chamber with modified RPMI 1 640 medium containing 10%fetal bovine serum.The cell concentration in the suspension was 2.0×107cells/ml.The cell suspension of 0.1 ml was injected in the retinal gap of the right eye in six New Zealand rabbits.The rabbits were immuno-suppressed with daily intramuscular injection of cyclosporin A so as to prevent spontaneous tumor regression.The dosage schedule was 15 mg/kg per day for 3 days before cell inoculation and for 4 weeks thereafter，which was followed by 10 mg/kg per day for the last week of the experiment.The rabbits were randomly divided into study group（n=3）and control group（n=3）.Under general anesthesia selective ophthalmic arterial perfusion was performed in all the experimental rabbits.Melphalan（2.5 mg）was diluted with saline to prepare 15 ml solution and the solution was then injected in a pulse type into the rabbits of the experiment group，while only 15 ml saline was injected into the rabbits of the control group.The tumor growth condition at 7 and 14 days after the treatment was determined，and the results were compared between the two groups. ResultsDuring the period when the injection of cyclosporin A was used，the rabbits showed mild side effects.The retinoblastoma model was successfully established in all six experimental rabbits.Super-selectivecatheterization was performed 7 times，of which successful catheterization of ophthalmic artery was obtained in 6.One week after selective ophthalmic arterial perfusion of melphalan the tumor size was significantly decreased，and the tumor disappeared within 2 weeks.In the control group，swelling and tears of the right eye was observed in one rabbit，which spontaneously disappeared in one week.ConclusionFor the treatment of retinoblastoma in rabbits，selective ophthalmic arterial perfusion of melphalan is feasible.The results of this study provide useful reference for further research on ophthalmic arterial perfusion for retinoblastoma.（J Intervent Radiol，2015，24：146-149）

【Key words】retinoblastoma；animal model；selective ophthalmic arterial perfusion；melphalan

成视网膜细胞瘤（retinoblastoma，RB）是儿童最常见的眼内原发恶性肿瘤，全球发病率约为1/ 15 000～18 000，不治疗的病死率高达100%［1-3］。近年来发达国家通过开展常规眼科筛查，早期诊断治疗，RB患儿5年生存率已达87%～99%［4］。发展中国家RB患儿往往因发现明显白瞳或斜视才就诊，延误了早期治疗时机，病死率仍高达39%［5］。

2008年，Abramson等［6］使用微导管从股动脉穿刺进入到眼动脉，直接将化疗药物灌注到眼动脉，取得了显著的治疗效果。……