原发性干燥综合征患者细胞因子途径、TOLL样受体信号途径相关基因表达的初步探讨  

Gene expression profiling reveals abnormal cytokine pathway, toll-like receptor signal pathway in patients with primary sjogren＇s syndrome

作　　者：王芳[1] 程永静[1] 黄慈波[1] 赖蓓[1] 

机构地区：[1]卫生部北京医院风湿免疫科,北京100730

出　　处：《临床内科杂志》2010年第3期200-202,共3页Journal of Clinical Internal Medicine

摘　　要：目的筛选原发性干燥综合征（pSS）患者的外周血单个核细胞的细胞因子途径、TOLL样受体信号途径的差异表达基因，并探讨其在发病机制中的作用。方法取3例初次发病的pSS患者及3例健康对照者的外周血单个核细胞，提取总RNA，反转录并进行体外扩增，分别用Cy5及Cy3荧光标记pSS组及对照组的cDNA样品，与寡核苷酸基因芯片进行杂交，运用LuxScan5．0图像分析软件将芯片图像信号转化为数字信号，然后以Cy5／Cy3的比值数据进行分析（SAM软件）寻找差异表达基因，并对差异表达基因用分子功能注释系统（MAS）进行处理。结果pSS组与对照组外周血单个核细胞中的细胞因子途径相关基因、TOLL样受体信号途径相关基因的表达差异有统计学意义（P〈0．01）。以上基因途径中基因TNFSF13B、CD40、TNFRSF7、CD86表达上调，基因FAS、CD40LG、CD80表达下调。结论pSS患者细胞因子途径和TOLL样受体信号途径的TN—FSF13B、CD40、TNFRSF7、CD86、FAS、CD40LG和CD80多个基因的异常表达提示pSS患者B细胞的激活、分化、凋亡和免疫耐受等多方面功能的异常，而且pSS的发病可能是多基因调控异常的结果，这些基因可能成为新的治疗靶点。Object The purpose of this study is to investigate cytokine pathway,Toll-like receptor signal pathway gene expression pattern of peripheral blood mononuclear cell （ PBMC ） between primary sjogren syndrome（pSS） patients and healthy controls. Methods The PBMC sample of 3 patients with sjogren syndrome and 3 healthy volunteers with consistent age were collected. The total RNAs was extracted from the PBMC samples, and reverse transcripted, in vitro transcription（ IVT）, labeled with CyS/Cy3 and hybridized on the gene chips. After scanning and data extraction with LuxScan 3.0, differentially expressed genes were analyzed with SAM method. The online tools of molecule analysis system （MAS） was used for biological knowledge mining. Results Statistical difference were calculated between the patient and control group in the following two pathways ： cytokine pathway, toll-like receptor signal receptor pathway. A- mong these,genes of TNFSF13B, CD40 ,TNFRSFT,CDs6 were up-regulated and genes of FAS, CD4o LG, CDso were down-regulated. Conclusion Abnormal genes expression of TNFSF13B, CD40, TNFRSF7, CDs6 ,FAS,CD40LG and CD80 in cytokine pathway and toll-like receptor pathway hints that B cell activation, differentiation, apoptosis and immune tolerance functions are aberrant in pSS patients. And the pSS is due to the multiple genes expression. The research may provide new target therapy for pSS.

关 键 词：原发性干燥综合征 基因芯片 单个核细胞 细胞因子 TOLL样受体 

分 类 号：R593.2[医药卫生—内科学]