1,25-二羟维生素D3对高危角膜移植急性排斥反应及角膜新生血管的影响

摘要/Abstract

摘要： 目的研究药物1,25-二羟基维生素D₃(二羟维D₃)在高危角膜移植模型中对免疫排斥反应及新生血管生长情况的影响,揭示1,25-二羟维D₃作为免疫抑制剂在角膜移植中的治疗作用及机制。方法建立大鼠高危角膜移植模型,按不同浓度的1,25-二羟维D₃(1×10^-5和1×10^-7mol/L)及环孢霉素A(CsA)分组,连续用药2周,观察移植物排斥情况并于术后4、7、14d取材行原位杂交等实验,分析各组细胞因子白介素1α(IL-1α)、肿瘤坏死因子-α(TNF-α)、血管内皮生长因子(VEGF)mRNA水平的变化情况。结果在1,25-二羟维D₃作用下,高危角膜移植物的存活时间明显延长;新生血管生长受抑制;合用CsA后效果更明显。原位杂交实验证实1,25-二羟维D₃能显著抑制植片IL-1α、TNF-αmRNA表达(P<0.01);对VEGF表达无直接影响。结论 1,25-二羟维D₃能有效地抑制新生血管生长及角膜移植急排期的免疫排斥反应,机制可能包括对前炎症因子(IL-1α、TNF-α)生成的抑制作用,而对VEGF无明显直接作用。

Abstract: Objective To investigate the effects of 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), a hormone that has immunosuppressive properties, on acute rejection and corneal neovascularization in rat keratoplasty model, so as to assess the therapeutic effects and explore the mechanism of 1,25(OH)₂D₃ as an immunosuppressant in corneal transplantation. Methods High risk corneal transplantation was performed orthotopically in SD rat models of high risk penetrating keratoplasty established by placing three 10-0 nylon sutures in the central corneas for two weeks, with the Wistar rats as the donors. The SD rat models were randomly assigned into 5 groups and treated with 1,25(OH)₂D₃ at varied concentrations and cyclosporine A (CsA). The expressions of interleukin (IL)-1α, tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF) mRNA were detected by in situ hybridization (ISH). Results 1,25(OH)₂D₃ significantly suppressed acute graft rejection and inhibited corneal neovascularization as compared with saline. 1,25(OH)₂D₃ showed better immunomodulatory effects when administered along with CsA in rat corneal allotransplants. ISH study demonstrated that 1,25(OH)₂D₃ strongly suppressed mRNA and protein expressions of the cytokines IL-1α and TNF- but not those of VEGF. Conclusion Topical administration of 1,25(OH)₂ D₃ can be effective in suppressing acute corneal graft rejection by inhibiting the expression of proinflammatory cytokines (IL-1α and TNF-α).

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党森涛, 陆晓和, 周瑾, 白浪. 1,25-二羟维生素D₃对高危角膜移植急性排斥反应及角膜新生血管的影响[J]. 南方医科大学学报, 2004, 24(08): 892-896,903.

DANG Sen-tao, LU Xiao-he, ZHOU Jin, BAI Lang. Effects of 1α, 25-dihydroxyvitamin D₃ on the acute immune rejection and corneal neovascularization in high-risk penetrating keratoplasty in rats[J]. Journal of Southern Medical University, 2004, 24(08): 892-896,903.

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1,25-二羟维生素D₃对高危角膜移植急性排斥反应及角膜新生血管的影响

Effects of 1α, 25-dihydroxyvitamin D₃ on the acute immune rejection and corneal neovascularization in high-risk penetrating keratoplasty in rats

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