抵挡汤干预对2型糖尿病大血管病变泡沫细胞焦亡的作用机制研究

2型糖尿病（T2DM）大血管病变具有发病早、病变范围广、程度重特点，以动脉粥样硬化为病理基础，炎症反应贯穿其始终。而细胞焦亡的发生伴随瀑布式炎症级联反应。泡沫细胞作为焦亡的靶细胞，在血管病变早期就已出现。中医学认为，脉络瘀阻是T2DM大血管病变的主要病机，以破血化瘀法论治。前期工作证实：该法代表方抵挡汤，可保护T2DM患者血管内皮，抑制T2DM大鼠大血管病变单核/巨噬细胞迁移、黏附、活化。据此提出假说：抵挡汤可抑制NLRP3炎症小体介导的泡沫细胞焦亡通路减轻炎症级联反应，延缓T2DM大血管病变发生、发展。本项目试图从整体水平动态观察、综合阐明抵挡汤抑制泡沫细胞焦亡减轻炎症级联反应，延缓T2DM大血管病变发生、发展的机制，并在离体水平多层次、多靶点地抑制和激活泡沫细胞焦亡信号通路，明确高糖环境下药物作用靶点。丰富破血化瘀法的理论内涵，所涉及的信号蛋白有望成为防治T2DM大血管病变的重要靶点。

The macrovascular complication of the Type 2 Diabetes Mellitus (T2DM) feature early onsets, wide lesions as well as high severity, with atherosclerosis pathological basis and inflammation going through. Nevertheless, the pyroptosis is accompanied by the waterfall inflammation cascade reactions. As the target of pyroptosis, the foam cell have already showed up in the early stage of vascular lesions. According to the Traditional Chinese Medicine,primary pathogenesis of the macrovascular complication is vein blood stasis resistance and the therapy is broke blood stasis. Our previous work has confirmed that the resistance of Didang decoction can protect T2DM patients’ vascular endothelium, and restrain the migration, adhesion and activation of mononuclear/macrophages in macrovascular complication of T2DM rats.Accordingly,the hypothesis that Didang decoction can delay the complication by restraining the pyroptosis of foam cells which can decrease the inflammation cascade reactions has been suggested.We aim to dynamic observation and clear the mechanism of Didang decoction delay the complication by restraining pyroptosis of foam cells.Explicit the target of the medicine by restraining and activating the foam cell pyroptosis signal way. This project can rich connotation of broke blood stasis,the reference signaling proteins will expect to become the target of macrovascular complication.