摘要
目的研究局部应用雷帕霉素(RAPA)滴眼液对大鼠角膜移植术后角膜白细胞介素-1β(IL-1β)、干扰素γ(IFN-γ)和穿孔素(PFP)mRNA表达的影响。方法建立大鼠穿透角膜移植动物模型,以SD大鼠为受体,Wistar大鼠为供体,随机分为4组。手术后第2d起分别以滴眼液基质、1%环孢素A(CsA)滴眼液、0.2%RAPA滴眼液、0.2%RAPA与1%CsA滴眼液联合滴眼,4次/d,连续用药至排斥反应发生。未发生排斥反应的动物模型,用药至术后42d终止实验。术后14d检测术眼角膜组织IL-1β、IFN-γ和PFPmRNA表达。结果各用药组角膜植片的存活率显著高于对照组(P<0.01);联合用药产生协同作用优于单独用药各组,角膜IL-1β、IFN-γ及PFP的mRNA表达均明显下降,与对照组相比差异有统计学意义(P<0.01)。结论0.2%RAPA滴眼液显著延长了大鼠角膜植片的存活时间,联合用药产生协同作用,显著抑制角膜组织IL-1β、IFN-γ及PFPmRNA的表达,是抑制角膜移植排斥反应的作用机制之一。
Abstract Objective To study the effects of topically administered rapamycin （RAPA） on the expression of corneal IL-1 β, IFN-γ, and PFP mRNA in rats after transplantation. Methods Fifty-five male SD rats were used as recipients,and 26 female Wistar rats served as donors. Penetrating corneal transplantation was performed in SD rats. Experimental rats were randomly divided into 4 groups. 100 p^L of ophthalmic solution solvent was utilized topically in control group 4 times per day from the 2nd day after operation until rejection happened; 100 μL 1% CsA ophthalmic solution was topically used in CsA-treated group; 100 μL 0. 2% RAPA ophthalmic solution was applied in the same way in RAPA-treated group, and the combination of 0. 2% RAPA ophthalmic solution 50 μL and 1% CsA ophthalmic solution 50 μL was administrated in RAPA and CsA-treated group. The experiment was ended on the 42 days after operation. The corneal grafts were inspected by slit-lamp microscope. IL-1 β, IFN-γ and PFP mRNA in corneas of the rats were assessed by quantitative reverse transcription polymerase chain reaction （RT-PCR） on the 14 days after operation. Results The survival rate of the corneal grafts in various treated group was statistically higher than that in the control group （P 〈 0. 01 ）. The survival rate of corneal grafts in RAPA and CsA-treated group was superior to CsA or RAPA alone （ P 〈 0. 01, P 〈 0. 05 ）. There was no statistical difference between RAPA-treated group and CsA-treated group （P 〉 0. 05 ）. IL-1 β, IFN-γ and PFP mRNA were weakly expressed in normal corneas but overexpressed in allografts with reject reaction within 14 days after operation （P 〈 0.01 ）. Expressions of IL-1 β, IFN-γ and PFP mRNA were faint in various treated groups in comparison with the control group （P 〈 0. 01 ）. Conclusion 0. 2% RAPA ophthalmic solution prolongs the survival time of corneal allografts. RAPA and CsA have a synergistic effect in suppressing rejection. Suppression of 0. 2% RAPA ophthalmic solution on the expression of corneal IL-1 β,IFN-γ and PFP mRNA is one of the mechanisms of inhibiting corneal transplantation rejection.
出处
《眼科研究》
CSCD
北大核心
2007年第11期850-853,共4页
Chinese Ophthalmic Research
关键词
雷帕霉素
穿透角膜移植
免疫排斥
滴眼液
大鼠
RAPA
penetrating keratoplasty
immunologic rejection
ophthalmic solution
rat
