动脉粥样硬化是一种慢性炎症过程,其发生发展过程中始终伴随着炎症反应，CRP、TNF-α、IL-6等炎症因子在动脉粥样硬化的发生发展中起重要作用。前期研究表明以益气活血化痰为原则的代表药物消溶稳斑方可以降低动脉粥样硬化大鼠的血清TNF-α、IL-6、CRP 等炎症因子水平，同时增加大鼠血管内皮细胞AMPK蛋白表达，但作用机制尚不十分清楚。我们推测以益气活血化痰为原则的代表药物消溶稳斑方能通过AMPK/SIRT1信号通路，调控炎症反应，防止易损斑块形成及破裂。为证实该假说，一是对ApoE基因敲除小鼠主动脉弓斑块观察、组织相关活性物质检测；二是对炎症损伤人脐静脉内皮细胞培养及干预。从器官-细胞-分子水平，以AMPK/SIRT1信号通路为主线，研究消溶稳斑方对炎症反应的影响，阐明其对不稳定斑块的作用机制，为益气活血化痰法稳定斑块及治疗动脉硬化不稳定斑块提供理论依据。

Atherosclerosis is a chronic inflammatory process,its occurrence and development process has always been accompanied by inflammation,CRP、TNF-α、IL-6 and other inflammatory factors play an important role in the development of atherosclerosis occurrence.Previous studies have shown Yiqihuoxue phlegm principle of stable plaque on behalf of drug dissolving party can reduce TNF-α serum atherosclerosis rat, IL-6, CRP and other inflammatory cytokines, and increased vascular endothelial cells in rats AMPK protein expression，but the mechanism is not clear.we hypothesize Xiaorong Wenban Fang can inflammation and prevent the formation and rupture of vulnerable plaque by influencing AMPK/SIRT1 signaling pathways.To confirm this hypothesis,first,we will found the mice model by the ApoE knockout mice,describe and isolate the aortic arch plaques,organize relevant active substance testing.Second we will culture the human umbilical vein endothelial cells injury model of inflammation,and intervented by serum containing.In this study we will study the influence of Xiaorong Wenban Fang on the inflammatory response, from the organ-cells-the molecular level,the AMPK/SIRT1 signaling pathway as the main line.Over all the completion of this study will help us understand the mechanism of its unstable plaque,providea theoretical basis in Yiqihuoxue phlegm methods stable plaque and unstable plaque in the treatment of atherosclerosis.

动脉硬化不稳定斑块破裂是发生多种心血管事件的病理基础，炎症反应是不稳定斑块形成及破裂的重要机制。已有研究表明中医药在防治动脉粥样硬化斑块方面具有多环节、多靶点发挥作用及副作用小等独特优势，但其具体调控通路与作用机制尚不明确，因此我们开展了动物在体实验和体外细胞实验研究。其中动物在体实验，通过对运用益气活血化痰法代表方消溶稳斑方干预后的ApoE基因敲除小鼠主动脉弓斑块进行观察，并对其外周血清中TNF-α、IL-6、CRP等炎症因子、主动脉弓组织中AMPK、SIRT1磷酸化水平以及IKKβmRNA、MMP-9mRNA的表达进行检测；而体外细胞实验，通过对消溶稳斑方干预后的炎症损伤的人脐静脉内皮细胞进行细胞周期与细胞凋亡观察，并对细胞中AMPK、SIRT1磷酸化水平以及IKKβmRNA、MMP-9mRNA的表达进行检测。实验结果显示：1、动物在体实验研究证实消溶稳斑方可通过调控AMPK/SIRT1通路来提高AMPK磷酸化及SIRT1的表达水平，降低SIRT1磷酸化水平，降低IKKβmRNA、MMP-9mRNA的表达量，减低炎症因子（TNF-α、IL-6、CRP）活性，起到减少炎症反应，保护血管内皮，稳定并缩小小鼠主动脉弓不稳定斑块的作用；2、体外炎症损伤人脐静脉细胞实验证实消溶稳斑方可通过提高受损的内皮细胞中AMPK磷酸化水平，降低SIRT1磷酸化水平，降低IKKβmRNA、MMP-9mRNA的表达来调节AMPK/SIRT1通路，从而拮抗炎症反应，起到减轻内皮细胞炎症损伤，保护内皮细胞的作用。实验最终结论初步证实消溶稳斑方可上调AMPK/SIRT1通路中AMPK磷酸化水平及SIRT1的表达来发挥其抑制动脉粥样硬化斑块及损伤内皮细胞中的炎症基因IKKβmRNA、MMP-9mRNA的表达，减少炎症反应，减轻内皮细胞损伤，减少斑块内泡沫细胞及脂质沉积，保护内皮细胞，稳定并缩小动脉粥样斑块。本课题初步阐明了消溶稳斑方防治动脉硬化不稳定斑块的调控通路与作用机理，为中医药稳定并缩小动脉粥样硬化斑块提供了实验依据，为防治冠心病不稳定心绞痛提供了新的思路和方法，具有重要的学术价值和临床指导意义。