程序性坏死，不同于凋亡和坏死，是一种新型可调控的细胞炎性坏死方式，近年研究发现其是动脉粥样硬化（AS）易损斑块形成、破裂关键病理机制之一。C-FLIP是程序性坏死的重要调节蛋白。清心解瘀方是根据“瘀毒致变”理论由陈可冀院士的经验方愈梗通瘀汤化裁而来，前期大样本临床研究表明其可降低不良心血管事件发生率，但作用机制尚不明确；课题组前期研究发现清心解瘀方可上调c-FLIP蛋白水平，并提示其机制与抑制程序性坏死、炎症有关。因此提出假说：清心解瘀方可能通上调c-FLIP抑制巨噬细胞程序性坏死及其引起的炎症，从而稳定AS易损斑块。针对假说，本项目拟体内与体外实验相结合，采用ApoE-/-小鼠和RAW264.7巨噬细胞模型，探索清心解瘀方对AS易损斑块的影响及其与c-FLIP和巨噬细胞程序性坏死的关系，揭示其作用机制，旨在为“瘀毒致变”理论提供更多科学依据，为中医药防治心血管疾病提供新思路。

Necroptosis, different from apoptosis or necrosis, is a recently identified new type of programmed and inflammatory cell death, which plays a critical role in the development and rupture of vulnerable atherosclerotic plaque. C-FLIP is an important protein in the regulation of necroptosis. Qingxin Jieyu formula was developed from Yugeng TongYu decoction of academician Keji Chen under the guidance of‘blood-stasis and toxin leading to events’theory. Results of a large clinical trial showed that Qingxin Jieyu formula reduced the incidence of adverse cardiovascular events, but its mechanism remained unclear. Our previous studies found that Qingxin Jieyu formula was associated with increased c-FLIP level, implying that its mechanism was related to inhibition of necroptosis and inflammation. Therefore, we hypothesized that Qingxin Jieyu formula may stabilize vulnerable atherosclerotic plaque by upregulating c-FLIP expression, and inhibiting macrophage necroptosis and inflammation caused by necroptosis. We aim to reveal mechanism of plaque stabilizing effects of Qingxin Jieyu formula by observing its effects on plaque stabilization, c-FLIP and macrophage necroptosis and inflammation in ApoE -/- mice and RAW264.7 macrophage through both in-vitro and in-vivo experiments. Results of this study will reveal mechanism of Qingxin Jieyu formula, which will provide more scientific evidence for the‘blood-stasis and toxin leading to events’theory, and therefore provide traditional Chinese medicine with novel methods to treat patients with cardiovascular disease.