从影响高密度脂蛋白功能及促进胆固醇转运探讨活血化瘀药（芎芍胶囊）抗动脉粥样硬化的作用机制

Reverse cholesterol transport (RCT) is a process that cholesterol in the cells is transported to the lever to expel from the body through metabolism, which is regulated by multiple proteins. The high dense lipoprotein (HDL) is an important condition for RCT. However, there is clinical evidence showing that the increasing level of HDL-C doesn't significantly slow the atherosclerosis progress or reduce the cardiovascular events. All the functions of HDL, including anti-inflammatory, anti-atherosclerosis and promotion for RCT, are only dependent on the particle subtypes and related zymoprotein, but independent of its total quantity level. There is no report on medicines effecting on the HDL particle subtypes and improving the process of RCT regulation. Our former studies discovered that Xiongshao Capsule (XCS), drugs for invigorating blood circulation and eliminating stasis, could promote RCT and protect the anti-inflammation function of HDL without increasing the HDL level, which has an exact effect on anti-atherosclerosis. It's speculated that the medicine can impact on the HDL subtypes and promote the process of RCT in multiple tissues. In this study, the AS rabbit model and induced foam cell model are used to observe the effects of XSC on affecting factors of the hypothesis including HDL particle types, cholesterol efflux rate, proteins related to HDL anti- inflammation and level of proteins related to RCT (ABCA1 ect.) in aorta, lever and other tissues, in order to illustrate the medicine play a role in regulating the HDL subtypes and lipid metabolism in multi-link for anti-atherosclerosis, which will provide the new mechanism of drugs for invigorating blood circulation and eliminating stasis for anti-atherosclerosis with theoretical and experimental basis.

胆固醇逆转运（RCT）是细胞胆固醇转运至肝脏经代谢排出体外的过程，受多种蛋白调控，其中高密度脂蛋白（HDL）是RCT重要条件，但临床研究显示HDL-C水平增加并未显著延缓动脉粥样硬化（AS）进展及降低心血管事件，HDL的抗炎、抗氧化及促进胆固醇转运能力主要依赖其颗粒亚型及相关酶蛋白，与其总体水平无关。但经检索未发现有关通过影响HDL颗粒亚型、促进RCT的药物研究报道。我们既往研究发现活血化瘀药（芎芍胶囊）不升高HDL水平时，仍可促进RCT、保护HDL抗炎功能，抗AS确切，推测其可能影响HDL颗粒类型并促进多组织RCT过程。本研究应用AS兔及诱导泡沫细胞模型，观察芎芍胶囊在体内外对HDL颗粒类型、胆固醇流出率、HDL抗炎相关蛋白及主动脉、肝脏等多组织RCT蛋白（ABCA1等）水平的影响，阐明其调控HDL亚组分、促进RCT抗AS的作用，为活血化瘀中药抗AS新机制提供理论及实验依据。

胆固醇逆向转运（RCT）是细胞胆固醇转运至肝脏经代谢排出体外的过程，受多种蛋白调控，这一过程已取代传统的单纯降脂、抗炎成为抗动脉粥样硬化（AS）研究新热点。经前期文献检索未发现能够通过多种相关蛋白相关机制促进RCT的药物尤其是中药复方研究报道。既往研究发现活血化瘀药（芎芍胶囊）抗AS作用确切，能够通过降低血脂水平、抗炎、保护血管内皮等机制抗AS。本研究在前期研究基础上应用AS兔模型，从AS血管病理形态学、AS炎症相关因子、RCT相关蛋白及蛋白基因表达、高密度脂蛋白（HDL）抗炎功能相关蛋白等多个方面观察芎芍胶囊通过促进细胞胆固醇转运，促进多靶点参与的RCT过程，保护HDL抗炎功能等多种机制从而抑制AS斑块形成，抗AS的作用，为活血化瘀中药抗AS新机制提供理论及实验依据。. 研究得出以下结论：1.芎芍胶囊能够抑制AS兔主动脉斑块形成，减少动脉壁细胞内脂质沉积。2.芎芍胶囊能够升高AS兔血清ApoA-1水平，降低TC、LDL、VLDL水平，通过调节脂质水平来实现抗AS作用；芎芍胶囊能够升高AS兔血清中HDL2水平，増加HDL成熟亚型颗粒的水平，影响HDL亚型分布。3.芎芍胶囊能够芎芍胶囊能够上调肝脏ABCA1 mRNA水平，促进HDL介导的RCT；降低血清MPO水平，从而保护HDL抗氧化作用，维持其运载脂质的功能；提高血清PON1水平，保护HDL不被氧化，保护HDL抗AS功能；上调肝脏LCAT mRNA水平，对HDL的合成和成熟有一定影响。4. 芎芍胶囊有效成分（川芎嗪、芍药苷）能够协同降低RAW264.7源性泡沫细胞内TC、FC，促进泡沫细胞胆固醇外流，从而发挥抗动脉粥样硬化作用。5.芎芍胶囊有效组分能够通过调节ABCA1、ABCG1相关通路表达，进而促进泡沫细胞胆固醇外流。6.芎芍胶囊有效成分（川芎嗪、芍药苷）能够协同减少泡沫化细胞产生的炎症因子TNF-α、IL-1β、MCP-1，具备一定的抗炎作用。. 通过以上研究结果，可以得出活血化瘀中药（芎芍胶囊）能够促进AS兔主动脉细胞胆固醇转运，通过主动脉及肝脏参与RCT过程的相关蛋白促进RCT过程从而减少主动脉细胞内脂质沉积，提出了活血化瘀中药抗AS的新机制。芎芍胶囊能够有效减少多种炎症相关因子的表达，抑制炎症反应，并因此保护了RCT过程的正常进行，为RCT过程的进一步研究提供了新方向。芎芍胶囊能够保护。