局部使用TNP-470后兔眼房水中药物分布及对兔高危角膜移植术后新生血管的影响

Distribution of TNP-470 in Rabbit Aqueous Humor and Its Effect on Neovascularization after High-risk Corneal Transplantation

目的探讨局部使用TNP-470[O-(氯乙酰氨甲酰基)烟曲霉醇]后兔眼房水中的药物质量浓度,观察其对兔眼高危角膜移植术后新生血管增殖的影响。方法健康新西兰白兔30只,其中10只兔角膜作为供体、20只兔进行高危角膜移植受体动物模型的制备。将成功建立高危角膜移植动物模型的16只兔按随机数字表法分为4组,每组4只:A组术后不用药,术后第1天B、C、D组分别予质量浓度为100、500、1 000ng.mL-1的TNP-470滴眼液,6次.d-1,1滴.次-1,共观察90d。用药后1、2、7、14、28、56d用高效液相色谱法(HPLC)检测4组兔眼房水中TNP-470的质量浓度;术后第2天开始隔日观察术眼新生血管长入情况,并在术后2、6、9、12周记录新生血管指数(NI)。结果 3组各时间点兔眼房水中均可检测到TNP-470,且各组药物质量浓度比较,差异有统计学意义(P<0.05)。术后2周A组NI一直呈上升趋势,6周后维持在较高水平;B、C、D组在术后6、9、12周一直维持在较低水平,与A组比较差异有统计学意义(P<0.05)。结论局部用TNP-470具有抑制兔眼高危角膜移植后新生血管增殖的作用。

Objective To investigate the concentrations of O-（chloracetyl-carbamoyl）fumagillol（TNP-470）in rabbit aqueous humor after local administration,and to observe the effect of TNP-470 on neovascularization after high-risk penetrating keratoplasty（PK）.Methods Corneal neovascularization was induced in 30 New Zealand white rabbits by NaOH.Donor corneas from 10 rabbits were transplanted into 20 recipients of corneal grafts.The animal model of high-risk corneal transplantation was successfully established in 16 rabbits.These rabbits were randomly divided into four groups,with 4 rabbits in each group.Group A was not given drug treatment.Group B,C and D were topically administered with TNP-470 at concentrations of 100,500 and 1 000ng.mL-1（1drop per time,6times per day）for 90 days,respectively.Drug concentrations in aqueous humor were measured by high performance liquid chromatography（HPLC）at 1,2,7,14,28 and 56 days after the start of drug treatment.Corneal allografts were examined every other day and neovascularization index（NI） were recorded at 2,6,9 and 12 weeks after transplantation.Results TNP-470 was found in aqueous humor at each time point,and there were significant differences in TNP-470 concentrations among the three experimental groups（P0.05）.In group A,NI increased at 2 weeks after transplantation and was maintained at a higher level after 6 weeks.However,NI was maintained at a lower level at 6 weeks after transplantation in group B,C and D.The differences were significant between experimental groups and group A（P0.05）.Conclusion Ophthalmic administration of TNP-470 can inhibit corneal neovascularization after high-risk corneal transplantation in rabbits.