IL-1ra和CsA对大鼠角膜移植物TRAIL及DR4表达的影响

Effects of IL-1ra and CsA on expression of TNF-related apoptosis-inducing ligand and its receptor DR4 in corneal allograft rejection in rats

目的比较研究白细胞介素-1受体拮抗剂(IL-1ra)和环孢素A(CsA)对急性排斥期角膜移植物肿瘤坏死因子相关凋亡诱导配体(TRAIL)及其死亡受体4(DR4)表达的影响。方法建立大鼠同种异体穿透角膜移植模型,设生理盐水处理组、CsA治疗组和IL-1ra治疗组。免疫组织化学法检测急性排斥期角膜植片TRAIL及DR4的表达,并以正常大鼠角膜作为对照。结果TRAIL及DR4在正常角膜中均有表达,主要分布于上皮层,基质层及内皮层有少量表达。急性排斥期角膜植片各层TRAIL及DR4表达均增高;与正常大鼠相比,生理盐水组TRAIL及DR4蛋白表达增高最为明显,CsA组次之,IL-1ra组TRAIL及DR4蛋白表达轻度增高。结论IL-1ra、CsA均可通过调节TRAIL及DR4的表达抑制角膜移植排斥反应,且IL-1ra的效果优于CsA。

Objective Recent studies implicated that there may be a close relationship between TRAIL/DR4 and transplant immune rejection. The purpose of this study was to explore the effcets of IL-1ra and CsA on the expressions of tumor necrosis factor（ TNF） -related apoptosis-inducing ligand （TRAIL）and its receptor DR4 in corneal allograft rejection in rats. Methods Corneal transplantation was performed orthotopically from 27 donor Wistar rats to 54 recipient SD rats,and 5 normal Wistar rats were as control. Normal saline solution（NS） , CsA eye drops and IL-1ra eye drops was utilized respectively in recipient rats of NS group,CsA group and IL-1ra group for two weeks. Immunohistochemistry staining was used to detect the expressions of TRAIL and DR4 protein in corneal allograft rejection. The corneal rejection was scored under the slit lamp, and rejection index was recorded. Results The survival time of corneal graft was （10.250 ± 1.055） days,（12. 917 ±0. 996） days and （16.667 ± 0. 888 ） days respectively in NS group, CsA group and IL-1 ra group,indicating the graft survival time was significantly longer in IL-1ra group than NS and CsA group（P 〈0. 01 ）. TRAIL and DR4 were expressed in normal corneal epithelium,showing the modest intensity of staining in corneal stroma and endothelium. Expressions of TRAIL and DR4 in IL-1ra group were markedly decreased in comparison with the NS group, however, the expression levels in IL-1ra group, CsA group and NS group were significantly increased in comparison with normal control （P 〈 0.01 ）. Conclusion 1L-1ra and CsA inhibit postoperative immunologic rejection and keratoplasty through TRAIL/DR4 pathway,and IL-1ra has better effectiveness than CsA.