干扰素诱导蛋白鼠p204及人IFI16对血管重构的影响及机制

The interaction between the cells of vessel wall and endovascular and the variety of cytokines between the cells have been established to play significant roles in the occurrence and development of vascular proliferative diseases such as atherosclerosis, hypertension, stent restenosis after percutaneous coronary intervention. The roles of vascular smooth muscle cells (VSMC ), vascular adventitia fibroblasts (VAF) and vascular endothelial cells (VEC) are particularly important. Use the vessel wall cells as intervention target and terminal adjustment has important clinical significance for preventing and treating vascular proliferative diseases .The study was to observe the expression of p204 and IFI16 in artery tissue and vessel wall cells, and to investigate the inductivity of interferons (IFN). Use the angiotensin II (Ang II) and transforming growth factor-β1 (TGFβ1) to induce VSMC and VAF activated, and basic fibroblast growth factor (bFGF) to activate VEC, respectively, then overexpression or knockdown of p204 or IFI16, to observe the biological functions of cell activation, proliferation, migration and collagen synthesized and its mechanism. At last the rat carotid balloon injury model was established to observe the mechanism of local transfection of p204 to reverse the vascular remodeling process. For new clinical applications of IFNs and interferon-inducible protein in the treatment of vascular proliferative diseases.

血管壁及血管腔内多种细胞和细胞内外各种细胞因子之间的相互作用在动脉粥样硬化、高血压、血管介入治疗术后再狭窄等血管增殖性疾病的发生、发展过程中起重要作用，其中血管平滑肌细胞(VSMC)、血管外膜成纤维细胞(VAF)及血管内皮细胞(VEC)的角色尤为重要。以上述血管壁成分细胞为干预靶点和调控终端，对防治血管增殖性疾病有重要临床意义。本项目拟观察p204及IFI16在血管组织及血管壁细胞的表达及干扰素(IFNs)诱导性；分别通过血管紧张素Ⅱ及转化生长因子β1诱导VSMC及VAF活化、通过碱性成纤维细胞生长因子刺激VEC活化，观察p204及IFI16过表达及沉默对细胞活化、增殖、迁移及合成胶原等生物学功能的影响及相关机制；并进一步构建大鼠颈动脉球囊损伤模型，观察p204局部转染对抗损伤血管增殖重构的作用及机制，为临床应用IFNs及干扰素诱导蛋白治疗血管增殖性疾病提供新的依据。

血管壁及血管腔内多种细胞和细胞内外各种细胞因子之间的相互作用在动脉粥样硬化、高血压、血管介入治疗术后再狭窄等血管增殖性疾病的发生、发展过程中起重要作用，其中血管平滑肌细胞(VSMC)、血管外膜成纤维细胞(VAF)及血管内皮细胞(VEC)的角色尤为重要。以上述血管壁成分细胞为干预靶点和调控终端，对防治血管增殖性疾病有重要临床意义。本项目观察鼠p204在大鼠VEC、VSMC及VAF细胞的表达及干扰素(IFN)诱导性，观察p204过表达及沉默对大鼠VEC、VSMC及VAF细胞周期、增殖、凋亡、迁移等生物学功能的影响及相关机制。并进一步培养人脐静脉内皮细胞（HUVEC）、人脐动脉和主动脉平滑肌细胞（HUASMC、HASMC）及人脑血管和主动脉外膜成纤维细胞（HBVAF、HAAF），检测p204同源蛋白人IFI16在上述细胞的mRNA和蛋白表达，观察IFI16过表达及沉默对上述细胞活化、增殖、迁移、凋亡等生物学功能的影响及相关信号通路变化，为研究 IFN及IFI16对抗损伤血管增殖重构及临床治疗血管增殖性疾病提供新的理论依据。