糖尿病性心筋症に対するＤＰＰ－４阻害剤の役割検討

检查 DPP-4 抑制剂在糖尿病心肌病中的作用

• 批准号: 13F03101
• 负责人: 南野 哲男
• 金额: $ 1.22万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2013
• 资助国家: 日本
• 起止时间: 2013 至 2015-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13F03101/
• 关键词: 糖尿病; 心不全; サイトカイン

Type 2 diabetes mellitus (T2DM) doubles the risk of major cardiovascular complications in patients with and without established cardiovascular disease, such that the majority of patients with diabetes die of cardiovascular diseases. Most of reported trials to date evaluating the effects on cardiovascular outcomes of specific glucose-lowering strategies or medications either have been insufficiently powered or have shown no significant cardiovascular benefit or an increased risk of death or heart failure. Hence, we plan to investigate the role of IL-33 in the modulation of left ventricular remodeling events in mice with heart failure following mechanical overload, since it has been reported that IL-33 induces protective effects in adipose tissue inflammation during obesity in mice (Miller AM et al., 2010). Myocardial functional parameters such as left ventricular dimension in diastole (LVDd) and systole (LVSd), intra ventricular septal diameter (IVSd) and posterior wall thickness (LVPWd) and fractional shortening (% FS) were assessed by echocardiography. Impaired cardiac function were noted in both in WT and IL-33-/- mice followed 8-weeks after TAC operation when compared to baseline, as evidenced by increased LVDd, LVSd, IVSd and LVPWd and reduced %FS. These parameters in IL-33-/- mice were improved compared with those in their WT-littermates.

2型糖尿病（T2DM）使患有或不患有心血管疾病的患者发生主要心血管并发症的风险增加一倍，因此大多数糖尿病患者死于心血管疾病。迄今为止，大多数报道的评估特定降血糖策略或药物对心血管结果影响的试验要么没有足够的动力，要么没有显示出显著的心血管益处，要么增加了死亡或心力衰竭的风险。因此，我们计划研究IL-33在机械负荷心力衰竭小鼠左心室重构事件的调节中的作用，因为有报道称IL-33在小鼠肥胖期间诱导脂肪组织炎症的保护作用（Miller AM et al., 2010）。超声心动图评价左室舒张期（LVDd）、收缩期（LVSd）、室间隔内径（IVSd）、后壁厚度（LVPWd）、缩短率（% FS）等心肌功能参数。与基线相比，TAC术后8周WT和IL-33-/-小鼠的心功能均受损，LVDd、LVSd、IVSd和LVPWd增加，FS %降低。与wt组相比，IL-33-/-小鼠的这些参数有所改善。