基于IL1β介导的血管壁炎性重塑研究Anakinra对颅内动脉瘤的疗效及作用机制

颅内动脉瘤的治疗现状仍需改善，以药物阻碍甚至逆转动脉瘤形成和进展，具备重要的研究意义。我们假设IL1β介导的平滑肌表型转换在颅内动脉瘤血管壁炎性重塑过程中起到重要作用，而Anakinra作为IL1β拮抗剂可能有抑制动脉瘤进展的疗效。本项目以大鼠颅内动脉瘤模型为体内实验基础，通过血管铸型电镜扫描和免疫组化等方法动态监测血管壁重塑过程，以Western Blot和PCR等手段检测IL1β的作用，并以Anakinra作为干预阻断措施，检验其治疗效果并验证IL1β的作用机制。同时，设计体外实验，以IL1β诱导人脑血管壁平滑肌细胞（HBVSMCs）表型转换，将其与人巨噬细胞（U937）在transwell中共培养，检验MCP-1分泌水平以及U937的活化迁徙。同时建立IL1受体、IL1β、MCP-1沉默细胞系，分组探索IL1β作用原理；再以Anakinra于体外阻断IL1β的作用，验证其机制。

Management of intracranial aneurysms still needs to be improved. It is of great significance to study drugs which can impede or even reverse the formation and progression of aneurysms. We hypothesis that IL1β mediated smooth muscle cell phenotype modulation may play a leading role in the inflammatory vascular remodeling of intracranial aneurysm, and Anakinra, as an IL1 receptor antagonist, may have therapeutic effect to suppress aneurysm progression.This protocol will use rat intracranial model to conduct in vivo study. The vascular remodeling process will be observed through immunohistological analysis and electron microscope scanning of vascular cast. The effect of IL1β will be tested by Western Blot and PCR. Anakinra is used to block IL1β and to exam therapeutic effect. In vitro study, IL1β is used to induce phenotype modulation of vascular smooth muscle cells (HBVSMCs), then it will be co-cultured with macrophages (U937) in Transwell, to test MCP-1 secretion and macrophages migration. And IL1R, IL1β, MCP-1 silencing cells are used to reveal underlying mechanism. Also, Anakinra will be examed in vitro.