IL-37/SIGIRR/TLR4轴调控动脉粥样硬化的机理研究

课题组前期研究证实，急性冠脉综合征患者血浆 IL-37 水平显著升高; TLR4/NF-κ B 通路介导重组 IL-37 减轻心肌缺血再灌注损伤效应。预实验表明重组 IL-37 显著延缓动脉粥样硬化（AS）进程，IL-10是其发挥抗AS的重要效应分子，但信号机制不明。最新研究证实，IL-37 的受体为单一免疫球蛋白白介素1受体相关蛋白（SIGIRR），后者通过负向调控TLR4活性转导信号。因此，我们提出 IL-37经SIGIRR /TLR4轴负向调控 AS 进程的假说。我们拟建立内源性IL-37干预 AS 模型，观察 IL-37/SIGIRR/TLR4 活性变化和斑块进展，并阻断关键分子SIGIRR、上调TLR4活性，初步阐明 IL-37在 AS 进程中的作用及机制。

We found that the plasma interleukin-37(IL-37) levels were siginificantly higher in patients with acute coronary syndrome than the control group, and recombinant human IL-37 ameliorated myocardial ischemia/reperfusion injury via the TLR4/NF-κB pathway.Our preliminary experiment revealed that recombinant human IL-37 significantly attenuated atherosclerosis in ApoE-/- mice via promoting the production of IL-10. More recently, researchers confirmed that the IL-37 receptor is SIGIRR, which signals through TLR4 resulting in reduced TLR4-mediated signaling. We hypothesized that IL-37 attenuates atherosclerosis via regulating the SIGIRR/TLR4 axis. We will dynamically observe the effect of endogenous IL-37 on the development of atherosclerosis. In addition, different approaches will be used to clarify the exact role of IL-37 in atherosclerosis.