协同刺激分子在单纯疱疹性角膜基质炎鼠外周血中的表达  

Expression of costimulatory molecules in peripheral blood of mice with herpetic stromal keratitis

作　　者：夏丽坤[1] 张劲松[2] 陈晓隆[1] 杨宏伟[1] 

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

出　　处：《眼科新进展》2006年第1期14-18,共5页Recent Advances in Ophthalmology

基　　金：辽宁省教育厅高等学校科学技术研究项目(编号:2004D163)

摘　　要：目的研究鼠单纯疱疹性角膜基质炎发生和发展过程中协同刺激分子在外周血中的表达水平,探讨协同刺激分子的表达与单纯疱疹性角膜基质炎之间的关系。方法用单纯疱疹病毒1型(herpessimplexvirustype1,HSV1)接种于BALB/c鼠角膜上建立单纯疱疹性角膜基质炎(herpeticstromalkeratitis,HSK)动物模型,分别于角膜接种病毒前和接种病毒后的第1d、3d、7d、10d、14d、21d及28d,用毛细管取小鼠的左眼眼眶静脉窦血1mL,提取淋巴细胞,用半定量逆转录聚合酶链反应检测协同刺激分子B71、B72、CD28、CTLA4的表达水平;同时,在裂隙灯显微镜下观察鼠角膜的临床变化。结果HSV1感染鼠的角膜后,小鼠均患了急性角膜上皮炎,并于感染后1周内痊愈。86.7%(78/90)的小鼠自感染病毒后第10d起开始出现角膜基质炎改变,典型的表现为灶状角膜基质混浊,局部角膜新生血管化,炎性细胞浸润。角膜基质混浊逐渐进展,于3周时达到高峰,4周时开始修复。鼠在感染病毒之前,外周血中表达微弱的CD28mRNA,不表达CTLA4、B71及B72mRNA。鼠感染病毒后,外周血中CD28、CTLA4和B71的表达量均显著增加,B72仍无表达;CD28在HSK的发生和发展过程中表达水平较高,在疾病愈合过程中表达减弱;B71表达的高峰时间是病毒感染后的3～21d,以稍低的表达水平平行于CD28的表达。结论在鼠单纯疱疹性角膜基质炎的发病过程中,协同刺激分子CD28/CTLA4:B71在外周血中的表达明显增强,在诱导CD4+T细胞介导的单纯疱疹性角膜基质炎中起关键性作用。Objective To investigate the expression of costimulatory molecules in murine peripheral blood during herpetic stromal keratitis （HSK）, and its relationship with HSK. Methods Corneals of BALB/c mice were inoculated with 1 × 10^6 PFU HSV-1 Mekrae strain to establish the HSK model. The levels of costimulatory molecules CD28/CTLA-4 ： B7 in peripheral blood of mice were detected by RT-PCR on the 0, 1st, 3rd, 7th, 10th, 14th, 21st and 28th day after corneal inoculation with HSV-1. Mice were examined by slit lamp biomicroscopy after infection. Results After inoculation of the cornea with HSV1 in BALB/c mice, epithelial damage was observed and healed within 7 days. At the 10th day, 86.7% of the mice developed stromal opacities, and opacification peaked on the 3rd week after inoculation with a decline thereafter. In semi-quantitative RT-PCR analyses, the expression of CD28, CTLA-4, BT-1 mRNA were notably higher during the development of HSK than those before inoculation, while B7-2 remained negative. The expressions of CD28 were relatively high during the pathogentsts and development of HSK, while decreased during agglutination. B7-1 levels peaked on the 3-21 day after inoculattorL The expression level of B7-1 was slightly lower than but Paralleled that of CD28.Conclusion The increase of costtmulatory molecules CD28/CT- LA-4：B7-1 expression in murine peripheral blood are closely associated with the activated CD4^＋ T cells-mediated HSK.

关 键 词：单纯疱疹病毒 协同刺激分子 外周血 

分 类 号：R772.2[医药卫生—眼科]