Th1、Th17细胞相关因子在实验性自身免疫性葡萄膜炎大鼠中的表达及作用

Expression and roles of Th1,Th17 cytokines in experimental autoimmune uveitis of rats

目的探讨辅助性T细胞(T helper cells,Th)1、Th17细胞相关因子在实验性自身免疫性葡萄膜炎(experimental autoimmune uveitis,EAU)中的表达及作用。方法取清洁级纯系健康雌性Lewis大鼠40只随机分为EAU组(32只)和对照组(8只),EAU组用光感受器间维生素A类结合蛋白诱导大鼠EAU模型,进行临床症状评分,免疫组织化学方法检测造模后视网膜内干扰素(inferferon,IFN)-γ、诱导型一氧化氮合酶(inducible nitric oxide synthase,i NOS)、白细胞介素(interleukine,IL)-17、IL-6的表达。ELISA法对比分析房水中各细胞因子的变化情况。结果 EAU模型建立成功;造模后第14天,视网膜损害以外层为主,视网膜内有大量炎细胞浸润,从而导致视网膜内结构紊乱,同时在视网膜的视锥、视杆细胞层和神经节细胞层i NOS、IL-17、IL-6、IFN-γ表达,细胞阳性率分别为29%、48%、52%、73%。在EAU发病过程中,IL-6于造模后第7天迅速升高,第10天达到高峰;IL-17于造模后第14天达到最高值,变化趋势与炎症进程一致;IFN-γ在炎症后期仍有升高,于造模后第16天达到最高值;IL-6、IL-17、IFN-γ与对照组相比,各时间点表达差异均有统计学意义(均为P<0.05)。i NOS在炎症进程中表达有所增加,但与对照组相比,各时间点的表达差异均无统计学意义(均为P>0.05)。结论Th1、Th17细胞相关因子调节网络共同参与实验性自身免疫性葡萄膜炎的发生发展。

Objective To investigate the expression and roles of Thl,Thl7 cytc kines in experimental autoimmune uveitis（EAU） of rats. Methods Forty clean healthy female Lewis rats were randomly divided into EAU group（ 32 cases）and control group（ 8 cases）, EAU was induced by immunization with interphotoreceptor retinoid-binding protein（IRBP） in EAU group, the clinical scoring were applied, immunohistochemistry was employed to detect the expression of IFN-γ,iNOS,IL-6,IL-17 in retina after estab- lishment of models. The cytokines levels changes in aqueous hμmor were observed and compared by ELISA. llhesullt Rat EAU models were constructed successfully. At 14 days after establishment of models, the retinal damage mainly located in the outer layer, and there was a large nμmber of inflammatory cells infiltrating the retina, which leaded to the retinal structural disorder, iNOS, IL-17 ,IL-6 and IFN-γ expressed in the cone, rod, and ganglion cell layers of the retina,the positive cell rates were 29% ,48% ,52% ,73% , respectively. During the course of EAU,IL-6 increased rapidly at 7 days after modeling, and reached the peak at 10 days;IL-17 reached the highest level at 14 days after model- ing,and the change trend was consistent with inflammation process. IFN-γ was still elevated in the late stage of inflammation and reached the highest level at 16 days after modeling;Compared with the control group, the expression of IL-6, IL-17 and IFN-γ were significantly different at each time point（ all P 〈0. 05）. The expression of iNOS in- creased in the inflammatory process, but the expression at each time point was not significantly different from the control group （ all P 〉 0.05 ）. Conelusion The cytokine regulating network of Thl and Th17 participate in the development of EAU.