大动脉炎活动期炎症因子筛选及其作用机制研究

The active stage of Takayasu arteritis (TA) involves many inflammatory factors, which is the key factor leading disease activity is still not clear. The objective of our study is to find out the key inflammatory factors, strive for realization: 1) high accuracy for the assessment of disease activity and severity, thus to guide the rational anti-inflammatory treatment; 2) to clarify the inflammation mechanism of the active stage of TA and explore new therapeutic targets.. This study intends to develop a broad-spectrum dynamic (active and remission stage) selection of inflammatory factors in a large sample TA cases. With using the patient's immune cells, vascular endothelial cells and vascular smooth muscle cells, and through the analysis of real time cell system, the pathological process during the occurrence and development of vascular inflammation in vitro will be explored dynamically, and a research platform that can simulate the vascular microenvironment of TA in vitro will be established. Then，we can select one or a group of inflammatory factors with the early or potential value of diagnosis related to disease activity of TA. At the same time, the expression of key factors related transcription factors will further be tested，in order to found more convenient and sensitive testing methods to judge the diease activity of TA. Such goals achieved will have a significant impact on the diagnosis or treatment of the active stage of TA, and improving the ability of management of TA tremendously.

大动脉炎（TA）活动期涉及众多炎症因子水平的变化，然而主导该期关键的炎症因子仍不清楚，本研究目标是在这些因子中遴选出关键因子，争取实现：1）可较准确评估炎症活动性和严重性，指导合理抗炎治疗；2）阐明该病活动期的炎症机制，探索新的治疗靶点。. 本研究拟开展大样本广谱动态（活动期、缓解期）的炎症因子遴选。在此基础上，利用患者的免疫细胞、血管内皮细胞和血管平滑肌细胞等，通过实时细胞分析系统，体外动态研究血管炎症发生、发展的病理进程，争取建立一个可以体外模拟TA的血管内微环境研究平台，遴选出一组具有诊断、预警潜力的TA活动期关键炎症因子。同时，进一步检测关键炎症因子相关转录因子的表达，探索是否可以找到更为简便、敏感的检测方法评判疾病的活动性。如果能达成这样的目标，将对TA活动期的诊治产生重大影响，极大提升TA的诊治水平。

大动脉炎（TA）是累及主动脉及其主要分支的慢性非特异性炎症疾病，炎症活动期涉及众多炎症因子水平的动态变化，然而主导炎症反应的关键炎症因子尚不清楚。本项目总体目标是筛选大动脉炎活动期关键的炎症因子，以期实现可较准确评估炎症活动性和疾病严重性，指导合理抗炎治疗并阐明大动脉炎活动期的炎症机制，探索新的治疗靶点。本项目利用临床样本和体外细胞培养实验，系统观察发现：（1）CCL2、CCL20、CXCL8、CXCL10、VEGF、IL-17E、PLGF、ANGIOPOIETIN-2、VEGF-D等细胞因子在大动脉炎活动期表达水平较慢性缓解期和健康对照明显升高，和传统炎症指标（血沉、CRP和hsCRP）水平明显相关，且对大动脉炎的活动性有较好的预测价值，抗炎治疗后这些细胞因子水平亦下降。（2）EBI3、IL12A、IL12B、IL28A、IL33、CXCL12、IL23A相关microRNA在大动脉炎患者中的表达量明显高于健康对照组。上述研究结果初步证实这些细胞因子和microRNA在大动脉炎发病及炎症活动中可能起到非常重要的作用，可用于指导疾病活动性评估和药物疗效评价。