项目名称: 汉防己甲素抑制腹主动脉瘤及其机制的实验研究
项目编号: No.81200226
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 医学一处
项目作者: 杨轶
作者单位: 四川大学
项目金额: 23万元
中文摘要: 腹主动脉瘤(AAA)以慢性炎性浸润和主动脉壁破坏性重构为主要的病理改变。促炎因子和基质金属蛋白酶(MMPs)能调节主动脉壁结缔组织的破坏,在AAA的发生和破裂过程中起着主要作用,核因子-κB (NF-κB)能够调节炎症变化和MMP的转录;血管平滑肌细胞(VSMCs)凋亡是主动脉血管重构最终导致动脉壁结构和功能异常的重要原因,VSMCs凋亡受半胱氨酸天冬氨酸蛋白酶(Caspase)-3的活化调节,而Caspase-3活化则依靠Ca2+。 前期研究发现汉防己甲素是一种钙离子拮抗剂, 有抑制NF-κB活化治疗溃疡性结肠炎的作用。本研究通过汉防己甲素(Tet)干预弹力蛋白酶诱导的小鼠腹主动脉瘤模型,研究Tet能否通过抑制NF-κB活化和(或)Caspase-3活化从而抑制AAA的形成和发展。本研究能完善汉防己甲素的药理机制,可以为临床治疗和干预AAA形成和发展提供科学依据。
中文关键词: 汉防己甲素;腹主动脉瘤;核因子-κB;凋亡;
英文摘要: Proinflammatory cytokines and matrix metalloproteinases (MMPs) are prominent mediators of the connective tissue destruction and inflammatory infiltration that characterizes abdominal aortic aneurysms (AAAs), and nuclear factor-kappa B(NF-κB) is a cytokine-responsive transcription factor that promotes macrophage MMPs expression. Vascular smooth muscle cells (VSMCs) apoptosis,which characterizes AAA, is induced by caspase 3 activation. Caspase-3 activity is Ca2+ dependent. Previous reports that tetrandrine (Tet) which is calcium channel blockers will ameliorate dextran-sulfate-sodium-induced colitis in mice through inhibition of NF-κB activation. The present experiment sought to determine whether Tet suppressed elastase-induced AAA formation and development in a mice model, along with inhibition of aortic wall NF-κB and (or) Caspase 3 activities, suggesting that targeting may be a novel therapeutic strategy for preventing expansion and rupture of AAA. If the hypothesis was confirmed, the present study suggests new therapeutic aspects of Tet to inhibit the progression of aneurysms.Both NF-κB and Caspase 3 is therefore a potentially important therapeutic target for the suppression of aneurysmal degeneration.
英文关键词: Tetrandrine;Abdominal aortic aneurysm;Nuclear factor-Kappa B;Apoptosis;