中文摘要：

目的 探讨来氟米特对大鼠自身免疫性葡萄膜炎（EAU）的保护作用.方法 实验研究.建立大鼠光感受器间维生素A类结合蛋白（IRBP）诱导的自身免疫性葡萄膜炎动物模型,按随机数字表法完全随机设计分组为正常组、模型组、来氟米特给药组（3、6、12 mg/kg）、环孢霉素阳性对照组（10 mg/kg）,每组6～8只.于造模第2天开始灌胃给药,每日1次,共13d.裂隙灯显微镜观察大鼠EAU的症状,造模后第14天制备大鼠眼球切片,以HE染色法进行组织病理学观察,参照Agarwal的标准对EAU各组大鼠进行临床症状和病理学分级进行评分,免疫组织化学染色（SP法）,检测各组大鼠眼组织中IL-17的表达,应用ELISA检测血清中IL-17和干扰素（IFN）-γ含量,使用流式细胞仪检测各组大鼠脾脏CD4＋ Th17细胞亚群纯度,使用逆转录-聚合酶链式反应（RT-PCR）检测各组大鼠眼组织IL-17 mRNA和IFN-γmRNA表达水平.计量资料的数据以均数±标准（差（（x）±s）表示,组间比较采用t检验.等级资料间比较采用非参数检验,多重比较用Bonferroni方法进行校正.结果 在来氟米特给药组的大鼠中,14d时EAU发病的临床评分均低于模型组,并呈剂量依赖性.与模型组比较[3（3,4）],来氟米特低剂量组[1.5（1,2）]临床评分明显减低,差异有统计学意义（P=0.0006,P＜α＇,α＇=0.05/15],病理学检查显示模型组大鼠眼部表现为重度炎症细胞浸润及视网膜全层破坏、受损,病理评分3（3,4）;中剂量组病理评分2（1,3）,明显低于模型组,差异有统计学意义（P=0.0014＜α＇,α＇=0.05/15）.免疫组织化学检查显示模型组虹膜、睫状体和视网膜部位可见IL-17蛋白表达,来氟米特各剂量组眼部IL-17蛋白表达明显减少.流式细胞检测发现,与正常组相比,模型组大鼠脾脏Th17细胞亚群比例显著升高（8.5％±1.3％vs.0.5％±0.2％;t=8.057,P=0.000＜α＇,α＇=0.05/15）,EAU大鼠口服不同?

英文摘要：

Objectives To investigate the protective efficacv of]eflunomide on the Lewis rats with experimental autoimmune uveitis （EAU）.Methods Complete randomized controlled trials research.Lewis rats were immunized with interphotoreceptor retinoid-binding peptide （IRBP） in order to build the model of EAU.Rats were randomized assigned into four groups, that is control group as A, model group without leflunomide as B, model group with leflunomide administrations as C, and model group with cyclosporine A as D.Rats in group C received intragastric administration of three doses of leflunomide at 3mg/kg/d;6mg/kg/ d;12mg/kg/d.Rats in group D received 10 mg/kg cyclosporin A were considered as a positive control.Each group has 6 to 8 rats.At the second day of immunization with IRBP, rats were intragastric administrated one time every day till day 13.Rats were investigated for EAU symptoms under slit lamp.Enucleated eyes were collected for sections with HE staining as histopathological evidences at the peak point of disease activity day 14.Treatment effectiveness was evaluated referred by Agarwal standard for clinical EAU and histopathological scoring.The expression of IL-17 in ocular sections was detected by immunohistochemistry （SP method）.The expression levels of IL-17 and IFN-γ in the serum were quantified by ELISA.Intracellular expression of IL-17 in the activated CD4＋T cells was assessed by flow cytometry.Ocular of rats were harvested and mRNA expression of IL-17 and IFN-γ were quantified through RT-PCR.Continuous variables were reported as mean ±SD.The comparison among groups was done by using analysis of students＇t test.Nonparametric test was used in Hierarchical data comparison and multiple comparison method was Bonferroni.Results The model of EAU disease was built successfully in Lewis rats.With giving IRBP for 14 days, the clinic EAU scores were lower in model rats than those without leflunomide.Moreover, the effects of leflunomide on the clinic EAU scores was dose-dependent.Comparing to vehicle-treate