从DNA甲基化及下游MAPK信号通路探讨活血解毒中药栀子川芎胶囊抗动脉粥样硬化的机理研究

Atherosclerosis (AS) is the pathological basis of many cardiovascular diseases. Abnormal DNA methylation involves inflammatory reaction, endothelial injury, smooth muscle cell proliferation, and foam cell formation, which plays a key part in the occurrence and development of AS. For the downstream signaling pathways, the activation of MAPK signaling pathway is an important factor in the progression of AS . Recent studies have shown that DNA methylation in AS is closely related to the downstream MAPK signaling pathway. Zhizi chuanxiong capsule was designed according to the theory of "stasis" and "toxin" . Preliminary experiments in vitro and in vivo showed that Zhizi chuanxiong capsule has a clear anti-AS effect. High-throughput sequencing showed that the drug could regulate AS gene methylation, and KEGG data analysis showed that the above genes were involved in MAPK pathway. Therefore, it is assumed that Zhizi chuanxiong capsule can achieve the anti-AS effect by regulating the level of gene methylation and thereby affecting the core protein expression of the downstream MAPK pathway. In order to verify this hypothesis, this study intends to adopt AS rabbit, foam cells and endothelial cell models, and use methylation PCR and protein expression techniques to reveal the new molecular mechanism of Zhizi chuanxiong capsule in the treatment of AS, so as to make a preliminary exploration for the development of methylation regulation drugs.

动脉粥样硬化（AS）为众多心血管疾病的病理基础。异常DNA甲基化涉及炎症反应、内皮损伤、平滑肌细胞增殖、泡沫细胞形成，是AS发生与发展的核心环节之一。在下游信号通路方面，MAPK信号通路的激活是AS疾病进展的重要因素。最近研究表明，在AS中DNA甲基化与下游MAPK信号通路密切相关。栀子川芎胶囊是根据瘀毒致病理论设计，前期体内外实验表明，栀子川芎胶囊抗AS效应明确。高通量测序手段发现该药能调节AS基因甲基化，KEGG数据分析发现，上述基因涉及MAPK通路。因此假设栀子川芎胶囊通过调节基因甲基化水平，进而影响下游MAPK通路核心蛋白表达从而实现抗AS效应。为验证此假设，本次研究拟采AS兔和体外细胞模型（泡沫细胞和内皮细胞模型），运用甲基化PCR及蛋白表达等技术，试图揭示栀子川芎胶囊治疗AS的新分子机制，为开发甲基化调控药物作前期探索。

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