细胞因子在鼠复发性单纯疱疹性角膜基质炎角膜组织中的表达  

Cytokine expression in murine cornea tissue during recurrent herpetic stromal keratitis

作　　者：夏丽坤[1] 张劲松[2] 陈晓隆[1] 王爱媛[1] 

机构地区：[1]中国医科大学附属第二医院眼科,沈阳110004 [2]中国医科大学附属第一医院眼科

出　　处：《中华眼科杂志》2005年第5期403-408,共6页Chinese Journal of Ophthalmology

摘　　要：目的探讨CD4+ T辅助细胞1型(Th1)和T辅助细胞2型(Th2)分泌的细胞因子在鼠复发性单纯疱疹性角膜基质炎(HSK )角膜组织中的表达水平,及其与复发性HSK的关系.方法制备复发性HSK的BALB/c鼠模型,用紫外线B光照射鼠的角膜诱导HSK复发;分别于紫外线照射前,照射后第3、7、10、14、21及28 天,取角膜中央直径为2 mm的角膜环,用逆转录聚合酶链反应(RT-PCR)检测Th1型细胞因子(IFN-γ、IL-12)和Th2型细胞因子(IL-4、IL-10)的表达水平.结果处于病毒潜伏感染期的小鼠经紫外线照射诱导病毒复发后,角膜基质混浊于紫外线照射后的7～14 d达到高峰;在此期间,IFN-γ、IL-12、IL-10和IL-4 mRNA在角膜组织中均有表达.其中,IFN-γ和IL-10在临床疾病的发生、发展过程中(病毒激活后第3～14天)高表达,在疾病恢复期(14 d后)表达减弱,与角膜基质混浊程度密切相关; IL-12是角膜组织内表达最丰富的细胞因子,在病毒激活后的第3天即开始高表达,高表达持续经过整个观察期;IL-4在病毒激活后的第3～14天有明显表达.结论在复发性HSK的角膜损伤早期,Th1型细胞因子和Th2型细胞因子同时表达于角膜组织中,与T细胞的免疫记忆性有关.IL-10的表达趋势平行于IFN-γ的表达,其表达水平与HSK的疾病程度密切相关.复发性HSK无法严格区分是由Th1细胞介导的还是由Th2细胞介导的,角膜的损伤与修复可能依赖于损伤性细胞因子和保护性细胞因子在病毒复发位置上的平衡.Objective To investigate the expression of cytokine in CD_4 + T helper type 1 (Th1) and T helper type 2 (Th2) cells in murine cornea during recurrent herpetic stromal keratitis (HSK) and its relationship with the HSK. Methods Seven weeks after corneal inoculation with HSV-1, the eyes of latently infected BALB/c mice were irradiated by UV-B and examined for the signs of inflammation and viral reactivation. The corneas of six mice with recurrent stromal disease and six controls were examined to detect the content of Th1 type cytokines(IFN-γ and IL-12)and Th2 type cytokines(IL-4 and IL-10)on days 0, 3, 7, 10, 14, 21 and 28 after irradiation. Results Peak of the inflammation process of HSK, manifested by stromal opacification, occurred 7-14 days after viral reactivation in latently infected mice. In semi-quantitative RT-PCR analyses, IFN-γ, IL-12 p40, IL-10 and IL-4 mRNA were expressed before and during the clinical course of recurrent HSK. The highest expression of IFN-γ and IL-10 was revealed during the occurrence and development of corneal inflammation (3-14 days after the reactivation of virus) with a decline at the recovering process (after 14 days). The expression of IFN-γ and IL-10 was co-related with the degree of corneal opacification. Large amounts of IL-12 p40 mRNA were detected in the cornea 3 days after the virus reactivation and maintained over the whole course of observation. IL-4 levels increased at 3-14 days after the reactivation of virus and declined after day 14. Conclusions Th1 and Th2 cytokines present together throughout the course of the inflammatory process accompanying recurrent corneal HSV-1 infection, which is likely associated with a memory response to viral antigens. The expression of IL-10 mRNA parallels with the expression of IFN-γ and is co-related with the degree of corneal inflammation. The damage and repair of corneal tissue in recurrent HSK may depend upon the balance between the destructive cytokines and protective cytokines at the site of virus reactivation.

关 键 词：单纯疱疹性角膜基质炎 角膜组织 复发性 TH1型细胞因子 TH2型细胞因子 逆转录聚合酶链反应 IL-4MRNA 紫外线照射 IFN-γ IL-10 Th2细胞介导 保护性细胞因子 T辅助细胞 IL-12 BALB/c 角膜基质混浊 HSK CD4^+ 疾病恢复期 

分 类 号：R772.21[医药卫生—眼科] R779.63[医药卫生—临床医学]