雷帕霉素纳米粒滴眼液治疗兔高危角膜移植排斥反应

Influence of rapamycin nanometer vector eye drops on high-risk corneal allograft survival

目的探讨雷帕霉素(RAPA)纳米粒滴眼液抑制高危角膜移植术后免疫排斥反应的疗效和机制。方法应用不同处理因素干预角膜移植术后免疫排斥反应,观察相关指标的变化。结果RAPA纳米粒滴眼液能明显延长角膜植片存活时间,并能使植片CD4+和CD8+T淋巴细胞表达时间延后。RAPA纳米粒滴眼液组植片中IL-2始终表达,而VEGF表达在14d开始被抑制。结论RAPA纳米粒滴眼液能延长高危角膜移植植片存活时间。

Objective Rapamycin（RAPA） is being concerned because of its stronger immunosuppressive effect and less toxicity to human tissue. Our study was to assess the immunosuppressive effect of RAPA nanometer vector eye drops on rejection of corneal allograft in rabbit model and its mechanism. Methods The corneal neovascular models were created in 94 New Zealand albino rabbits using cautery of 2 mol/L NaOH and divided into 5 groups. Group A（ 17 eyes） was as control group with the 9 donors of New Zealand albino rabbits and 17 recipients from New Zealand albino rabbits, The corneal donor grafts from 34 gray rabbits were implanted to 68 recipients of New Zealand albino rabbits with corneal neovascularization. The recipients eyes from group B were not treated as controls. The nanometer vector eye drops without RAPA was used twice a day for 28 days in group B. 1% RAPA eye drops was topically administrated 3 times per day for 28 days in group C ,and 0.5% RAPA eye drops of nanometer vector was treated twice a day for 28 days in group E. Postoperative evaluation of grafts included slit-lamp biomicroscopy and immunohistology,and IL-2 and VEGF in corneal tissue were detected by RT-PCR,respectively. Results The mean survival time of grafts in group A was （ 100.0 ± 0.0） days, and that in group E （45.22 ± 5.52 days） was statistically significant prolonged compared with group B（ll. 11 ± 1.69 days） ,group C （ 11.78 ± 3.19 days） and group D（ 17.78 ± 8.41 days） （ F = 562. 757 ,P = 0. 000）. The grafts in group E appeared an delayed immune response, showing delayed infiltration of CD4 , CDs T lymphocytes compared with group B, group C and group D. The gene expression of IL-2 was not inhibited but VEGF was suppressed 14 days later in group E compared with group B, group C and group D. Conclusion The topical application of RAPA eye drops of nanometer vector can prolong the survival time of corneal grafts.