声动力治疗通过增强巨噬细胞自噬促进炎症消退和凋亡细胞清除而稳定动脉粥样硬化斑块

Acute cardiovascular events in patients caused by atherosclerotic plaques rupture seriously endanger human being's health. In response to the current shortcomings of conventional treatments,our group took the lead to treat atherosclerotic plaques with sonodynamic therapy (SDT), a non-invasive targeted treatment, and found that SDT can significantly reduce plaque size, lipid and macrophage contents and inflammation, promote macrophage chemotaxis and migration and enhance macrophage autophagy. Malfunctions of lipid metabolism and apoptotic cell clearance, due to abnormal macrophage autophagy, are mainly responsible for plaque progression. We speculate that SDT may play a role while in the treatments of plaques by enhancing autophagy, which might recover the insufficiency of autophagy in advanced plaques. This project proposed, using THP-1 derived macrophage model, and related autophagy inhibitor and siRNA interference, combined with Western blot, Real-time PCR, ELISA, and transmission electric microscope and immune fluorescence technology, aims to research and confirm: 1)SDT reduce macrophage inflammatory response by enhancing autophagy; 2)SDT promotes apoptotic cell clearance by enhancing autophagy. This project proposed is interdisciplinary research among science, technology and medicine, and there are great theoretical significance, important clinical implications and broad industrialization prospects.

由动脉粥样硬化斑块破裂所引起的急性心血管事件严重危害人类健康。针对目前常规治疗手段存在的不足，本课题组率先尝试将无创伤、靶向性的声动力治疗（SDT）应用于斑块，发现SDT可显著减小斑块、降低巨噬细胞和脂质含量、减轻炎症、促进巨噬细胞趋化和迁移、增强自噬等。脂质代谢和凋亡细胞清除障碍是斑块进展的主要原因，这些都与自噬异常有关。我们推测SDT通过增强自噬可能弥补了进展期斑块自噬不足而发挥治疗作用。 本项目拟通过THP-1巨噬细胞模型，采用相关抑制剂和RNA干扰，结合蛋白印迹、ELISA、免疫荧光及电镜等技术研究证实：①SDT通过诱导自噬促进巨噬细胞炎症消退；②SDT通过诱导自噬促进凋亡巨噬细胞的清除。 本课题属于理工医多学科交叉项目，有重要的理论意义、较高的临床应用价值和广阔的产业化前景。

由动脉粥样硬化斑块破裂所引起的急性心血管事件严重危害人类健康。针对目前常规治疗手段存在的不足，本课题组率先尝试将无创伤、靶向性的声动力治疗应用于斑块治疗研究中。本项目通过THP-1来源的巨噬细胞模型和APOE敲除小鼠动脉粥样硬化斑块模型，采用自噬抑制剂3-MA和CQ，结合蛋白印迹、免疫荧光及免疫组织化学等技术研究证实声动力治疗所诱导自噬在以下几个方面发挥重要作用：（1）抑制导致THP-1巨噬细胞炎症的重要相关炎症因子Caspase-1和IL-1β的激活，抑制小鼠动脉粥样硬化斑块Caspase-1 p20的表达；（2）促进SDT处理后的THP-1巨噬细胞所引起的吞噬细胞迁移能力的增强，促进SDT处理后的巨噬细胞被吞噬细胞吞噬清除能力的增强。本项目属于理工医多学科交叉项目，所获得的研究成果对开展进一步研究具有重要的理论指导意义。