结膜下注射卡铂和环孢素联合治疗视网膜母细胞瘤的实验研究

Preclinical Study of Subconjunctival Injection of Carboplatin Combining with Cyclosprin A for Retinoblastoma Treatment

【目的】观察结膜下注射卡铂治疗视网膜母细胞瘤(RB)的疗效和环孢素(CsA)对卡铂治疗RB的增效作用。【方法】40只RB成瘤裸鼠分8组(G1～G8),对照组(G1)结膜下注射生理盐水,全身用药组(G2)腹腔内注射卡铂350μg+环孢素1.0mg,G3～G5组及G6～G8组分别结膜下注射卡铂100、200、350μg及卡铂100、200、350μg+CsA1.0mg,每周2次共3周。每天裂隙灯观察前房肿瘤情况并照相,第6周取眼球及结膜、巩膜作病理及图像处理,计算肿瘤面积及肿瘤抑瘤率。【结果】G2、G3、G6组肿瘤生长较G1组减缓,肿瘤未能控制。G4组肿瘤生长延缓,肿瘤控制率为40%。G5及G7组肿瘤无继续增大,部分肿瘤体积减少,肿瘤控制率和治愈率为60%和20%,G8组肿瘤全部控制,肿瘤控制率和治愈率为20%和80%,肿瘤基本消失。结膜下注射部位结膜和巩膜检查未见异常。图像处理及统计学分析显示,G3、G4、G6肿瘤面积和抑瘤率与G2之间无显著性差异(P>0.05),G5、G7、G8组肿瘤面积和抑瘤率与G2之间有显著性差异(P<0.05)。【结论】结膜下注射卡铂能在较低剂量下抑制RB生长,加用CsA能提高卡铂治疗RB疗效。结膜下联合注射卡铂和CsA是一种安全有效的RB化疗方法。

[Objective] To evaluate the effect of subconjunctival administration of carboplatin and the inhibitory effect of cyclosprin A combining with carboplatin for the treatment of retinoblastoma （RB）. [Methods] Forty nude mice were divided randomly into 8 groups （G1-G8） equally. In GI, normal saline （NS） was injected subconjunctivally as control. In G2, the systemic administration group, 350 μg carboplatin combining with 1.0 mg cyclosprin A （CsA） was given intraperitoneally. In G3-G5, single carboplatin was injected subconjunctival at the dosage of 100, 200, and 350 μg, respectively. In G6-G8, 100, 200, and 350 μg of carboplatin combining with CsA 1.0 mg in each was administrated subconjunctivally. All the injections were performed twice a week and lasted for 3 weeks. The areas of the tumors and the inhibitory rates were measured and the results were analyzed statistically. [Results] ① The tumors in G2, G3, and G6 were not inhibited but developed slowly compared with those in G1. The tumors in G4 increased slowly and the tumors inhibitory rate was 40%. The tumors in G5 and G7 were reduced or kept stable. The inhibitory rates and the cure rates were 60% and 20%, respectively. Tumors in G8 were reduced with a 20% inhibitory rate and an 80% curing rate. The RB tumors in anterior chamber disappeared mostly in G8. ② Pathological examination showed that there were no disorders found in the injection sites of conjunctiva and sclera. ③ The image analyzing was used to measure the tumor areas and the tumor inhibitory rates. No significant difference of the tumors areas and tumors inhibitory rates in G3, G4, G6 were found compared with those in G2 （P〉0.05）. While in G5, G7, G8, the tumors areas decreased and the tumors inhibitory rates increased significantly compared with those in G2 （P〈 0.05）. [Conclusions] The data indicate that subconjunctival delivery of carboplatin have better effect on the control of RB than systemic delivery, CsA enhances the inhibition effect of carboplatin and the combination injection of carboplatin and CsA subconjunctivally may be an effective and safe way in RB treatment.