TUG1通过介导血管炎症反应在烟雾病发病机制中的研究

Surgery is the main treatment for Moyamoya disease(MMD),but there still have many patients with poor prognosis,we also have little understand of the pathogenesis of MMD. In our preliminary study, we found that the levels of IL-1β in plasma were increased and the cox-2 expression was positive in the intracranial blood vessel wall,which meaned that inflammatory response may play an important role in the pathogenesis of MMD. At the mean time the overexpression of Taurine-Upregulated Gene 1(TUG1) can protect the cold injury in liver transplantation by inhibiting the inflammatory reaction, while the research group found that the TUG1 lentiviral vector was transfected into vascular smooth muscle cells, the inflammatory factor IL-1β , Cox-2 expression was significantly reduced, so we speculated that TUG1 in the pathogenesis of Moyamoya may play an important role. This study was to analyze the effect of TUG1 on the pathogenesis of Moyamoya by analyzing the changes of inflammatory factors after downregulation of TUG1 expression in the vascular smooth muscle，and to find a theoretical basis for finding new methods of treatment of Moyamoya.

手术是目前治疗烟雾病的主要方式，然而术后五年随访显示仍有许多患者远期预后不佳，对烟雾病的发病机制也知之甚少。课题组前期工作发现，烟雾病患者血浆中IL-1β水平增高，颅内血管壁上存在COX-2的阳性表达，提示免疫炎症反应在烟雾病病情进展中可能起重要作用。最新研究表明牛磺酸上调基因1（TUG1）过表达可通过抑制炎症反应来保护肝移植中冷损伤，而课题组在前期工作中发现将TUG1慢病毒载体转染血管平滑肌细胞，炎症因子IL-1β，COX-2的表达水平明显降低，因此课题组推测TUG1在烟雾病发病机制中可能起重要作用。本项研究拟通过干扰TUG1在烟雾病血管平滑肌中的表达后检测炎症因子的变化，确定TUG1在烟雾病发病机制中的作用，为寻找烟雾病的治疗的新方法寻求理论依据。

烟雾病发病机制复杂，对其发病机制知之甚少。目前以手术为治疗烟雾病的主要方式，暂无有效内科治疗手段，然而术后五年随访显示仍有许多患者远期预后不佳。近年来研究表明血管内壁炎症反应可能是导致推动烟雾状血管生成的重要因素，而本课题组在前期工作中发现本研究组首先发现烟雾病颅内血管壁上存在COX-2的阳性表达，用缺血缺氧刺激小鼠海马细胞(HT22)可以导致COX-2的表达增高而通过敲低核内TUG1后的COX-2表达降低，结合COX-2在烟雾病患者血浆中含量增加，推断TUG1介导的炎症反应在烟雾病进展中起重要作用。多项实验显示TUG1过表达可通过促进缺血过程中的炎症反应，在实验中我们发现敲除TUG1能明显抑制小鼠海马细胞缺血缺氧刺激后的COX-2的表达。据此本项目拟通过分析干扰TUG1前后烟雾病各种相关炎性因子表达的变化，探讨TUG1能否起到防止炎症的进展的作用，并试图阐明其分子机制，为寻找烟雾病新型术后辅助药物提供理论和实验依据。