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机构地区:[1]第一军医大学珠江医院眼科,广东广州510282
出 处:《第一军医大学学报》2004年第8期892-896,903,共6页Journal of First Military Medical University
基 金:广东省自然科学基金(020071)~~
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。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)-1γ, tumor necrosis factor (TNF)-γ, 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-1γ 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-1γ and TNF-γ).
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