二羟维生素D_3对高危角膜移植后存活率的影响

Effects of dihydroxyvitamin D_3 on the survival rate of high risk keratoplasty

目的:研究药物1,25(OH)2D在高危角膜移植模型中对移植物存活率3及免疫排斥反应的影响,揭示1,25(OH)2D作为免疫抑制剂在角膜移3植中的治疗作用及机制。方法:建立高危角移模型,分组给予不同含量的1,25(OH)2D,环孢霉素3A(CsA)免疫抑制剂等,观察疗效并于预定时间取材行原位杂交等实验,分析用药后IL-1α,TNF-α,VEGFmRNA水平的变化情况。结果:在1,25(OH)2D作用下,高危角膜移植物的存活时间明显延长;3合用CsA后效果更明显。原位杂交实验证实1,25(OH)2D能显著抑制3植片IL-1α,TNF-αmRNA表达;对VEGF表达无明显影响。结论:1,25(OH)2D能有效地抑制高危角移后急性期免疫排斥反应,延3长移植物存活时间,机制可能包括它对前炎症因子(IL-1α,TNF-α)生成的抑制,而与血管生长因子VEGF无明显关系。

AIM:To investigate the effects of 1, 25 Dihydroxyvitamin D3[1,25(OH)2D3] on the survival rate of allograft and the immunological rejection of high risk corneal transplantation model, and to reveal the therapeutic effects and mechanism of 1,25(OH)2D3 as an immunosuppressive agent in corneal transplantation. METHODS:High risk corneal transplantation model was established. All the groups were given 1,25(OH)2D3 and cyclosporine A(CsA) immunosuppressive agent of different contents. The effect was observed and the model was taken at predefined time for hybridization in situ experiment. The changes in the levels of interleukin 1 alfa(IL 1α), tumor necrosis factor alfa(TNF α), and vascular endothelial growth factor(VEGF)mRNA expressions were analyzed. RESULTS: The survival time of high risk corenal allograft was significant prolonged by using 1,25(OH)2D3, and it was more significant after association with CsA. The hybridization in situ experiment could demonstrate that the expressions of IL 1α and TNF α mRNA could be suppressed by using 1,25(OH)2D3. There was no significant effect on VEGF expression. CONCLUSION: 1,25(OH)2D3 can be effective in suppressing acute immunological rejection after high risk corneal transplantation and prolong the survival time of corneal allograft. The mechanism may include the inhibitive role in proinflammatory cytokines (IL 1α,TNF α) and have no remarkable relation with VEGF.