雷帕霉素免眼房水及血液中药物分布及防治免高危角膜移植后新生血管增殖的研究

目的 探讨雷帕霉素（RAPA）全身和局部使用后兔眼房水及血液中药物含量;观察其对兔眼角膜新生血管增殖的影响.方法 健康新西兰白兔30只,其中20只制作高危角膜移植受体动物模型.将16只兔随机分为4组,每组4只.A组术后不用药,B组涂RAPA眼膏1次/d,C组注射0.5%RAPA豆油注射液2.5mg/kg,2次/d,D组注射0.5 %RAPA豆油注射液1.5mg/kg,2次/d.术后观察90d.用药后1、2、7、14、28、56d高效液相色谱法（HPLC）检测4组兔房水及血液中RAPA 浓度.术后观察术眼新生血管长入情况并记录新生血管指数（NI）,共90d.结果 4组兔各时间点房水及血液中均可检测到RAPA,各组浓度间存在统计学差异.A组术后NI2周后一直呈上升趋势,6周后维持在较高水平;B、C、D组NI一直维持在较低水平.结论 全身或局部用RAPA具有抑制兔眼高危角膜移植后新生血管增殖作用,局部用药优于全身用药.

Rapamycin in Prevention of High Risk Corneal Allograft Neovascularization in Rabbits

Objective To investigate concentration of rapamycin in rabbit aqueous humor and blood after ophthalmic administration or injection,and antiangiogenesis effect of RAPA in high risk rabbit of penetrating keratoplasty（PK）. Methods Corneal vascularization was induced in 30 New Zealand white rabbits by NaOH.20 rabbits with corneal neovascularization byond three quadrants were received a unilateral 7mm diameter central PK. The 16 rabbits were divided into four treatment groups：Group A,control group with no therapy;Group B,ophthalmic administrated rapamycin ointment once a day;Group C,2.5mg/kg RAPA solution injection two times a day;Group D, 1.5mg/kg RAPA solution injection two times a day;Drug concentration in aqueous humor and blood were measured at l, 2, 7, 14, 28, 56d by HPLC.The cornea allografts were examined for 90 days and neovascularization index（N0 were recorded. Results Drug concentrations in aqueous humor and blood were measured by HPLC of four groups.NI among four groups were significantly different.Neovascularization in Group A yperplasia faster than Group B, C and D. Conclusions Ophthalmic administration or injection of RAPA can inhibit cornea nevascularization in rabbit model.However,ophthalmic administration is better than injection.