来氟米特活性代谢物A771726对大鼠角膜移植排斥反应的影响  

Effects of active metabolite of leflunomide A771726 on rat cornealallograft rejection

作　　者：郝念[1] 张明昌[1] 边芳[1] 

机构地区：[1]华中科技大学附属协和医院眼科,武汉430022

出　　处：《眼科研究》2009年第2期100-104,共5页Chinese Ophthalmic Research

摘　　要：目的探讨来氟米特活性代谢物A771726对大鼠角膜移植排斥反应的抑制作用。方法建立SD-Wistar大鼠同种异体穿透角膜移植模型,随机分组。A组为空白对照组;B、C、D组分别为0.5%、1.0%及2.0%A771726滴眼液组;E组为Wistar大鼠自体移植对照组。术后比较各组角膜植片排斥指数(RI)及植片存活时间,并对植片进行组织学及免疫组织化学染色观察。结果A组角膜植片存活时间为(9.38±2.26)d,B组(10.13±2.41)d,C组(17.57±1.72)d,D组(17.50±2.14)d,E组(>28.00)d。A组、B组分别与C组、D组植片存活时间差异有统计学意义(P<0.01)。移植术后10d,A组、B组角膜植片发生排斥反应,植片高表达IFN-γ及ICAM-1;术后20d,C组、D组植片发生排斥反应,植片IFN-γ及ICAM-1表达增高。结论局部应用A771726滴眼液能有效抑制角膜移植排斥反应。Objective Allograft rejection is the leading cause of corneal graft failure,so immunosuppressive agents are still in search for prevention of corneal transplantation rejection. Present study was designed to explore the inhibitory effects of A771726 eye drops, an active metabolite of leflunomide, on corneal allograft rejection. Methods The penetrating corneal transplantation model was established from 24 donor SD rats to 60 receiptor Wistar rats. Wistar rats were randomly divided into group A, B,C and D. The model rats from group A were as blank control group, and the model rats from group B, C and D were topically treated with different concentrations of A771726 （0. 5% , 1.0% and 2.0% , respectively）. The normal salt solution was topically used in the autograft model rats from group E. The response of cornea graft was clinically examined regularly under the slit-lamp microscope. The graft survival time and rejection index（RI） were recorded and compared among different groups. IFN-3, and ICAM-1 expressions in corneal graft were detected by immunohistochemistry. Results The average graft survival time was （9.38 ±2.26）d in group A, （10. 13 ± 2.41） d in group B, （ 17.57 ± 1. 72）d in group C, （17.50 ± 2.14） d in group D and over 28 d in group E,indicating a longer survival time in group C and D compared with group A and group B （ P 〈 0.01 ）. However, no statistically significant difference in graft survival time between group C and group D （ P 〉0. 05 ）. IFN-γ and ICAM-I in corneal grafts were overexpressed in group A and B on the lOth day after operation,and expressions of IFN-γ and ICAM-1 in group C and D were increased obviously on the 20th day after operation. Conclusion Topical application A771726 could effectively suppress allograft rejection in rat models.

关 键 词：A771726 来氟米特 角膜移植 免疫排斥 

分 类 号：R779.65[医药卫生—眼科] R988.1[医药卫生—临床医学]