血栓闭塞性脉管炎中IL6/JAK2/STAT3对ICAM-1和VCAM-1表达和调控机制的实验研究

Thromboangiitis obliterans (TAO) is an inflammatory disease, affecting the small- and medium-sized arteries and veins. So far, tobacco cigarettes are identified as a certain factor in the prognosis of TAO. In the pathogenesis of TAO, endothelial cells play a key role in initiation and perpetuation of vasculitis lesions through mediating intercellular adhesions between immunocytes as well as inflammatory cells and endothelial cells. Briefly, tobacco cigarettes induce the release of inflammatory cytokines that trigger some signaling pathways in endothelial cells to promote adhesions of immunocytes and inflammatory cells to endothelial cells, resulting in vasculitis lesions and intravascular thrombosis. It has been confirmed that the level of IL6 in serum of TAO is significantly higher as compared with healthy control individuals. Thus, it was first determined whether the higher levels of cytokines including IL6 were accompanied by enhanced ability of endothelial cells to adhere and vasculitis lesions in TAO patients. In vitro, together with our recent study on IL6/JAK2/STAT3 pathway, we determined whether IL6 could activated JAK2/STAT3 in endothelial cells and how IL6/JAK2/STAT3 pathway modulated the expressions of the two adhesion molecules, intercellular adhesion molecule-1（ICAM-1）and vascular cell adhesion molecule-1（VCAM-1）, and elucidated the underlying mechanisms, further providing a novel insight into treatments of TAO patients.

血栓闭塞性脉管炎是一类影响中、小动静脉的外周血管炎性疾病。目前，吸烟是导致血栓闭塞性脉管炎的确定因素。在血栓闭塞性脉管炎的发病机制中，内皮细胞发挥“始动性”和“持续性”作用，主要方式为通过介导免疫细胞和炎细胞黏附内皮细胞参与血管炎性病变。简言之，烟草促进多种炎性细胞因子释放，作用于内皮细胞后启动相关信号通路介导炎细胞和免疫细胞“黏附”内皮细胞，参与血管炎性病变以及血栓形成。研究中已经证实，血栓闭塞性脉管炎患者血清中IL6水平明显增高。因此，本课题首先检测血栓闭塞性脉管炎患者血清中高表达细胞炎性因子包括IL6是否伴随内皮黏附能力增强以及血管炎性病变；在体外实验中，结合我们近期对IL6/JAK2/STAT3通路的研究成果，验证IL6/JAK2/STAT3如何对两类重要的内皮细胞黏附分子ICAM-1和VCAM-1的表达进行调控，并对可能的机制予以揭示，为临床治疗血栓闭塞性脉管炎提供新的理论依据。