丹参多酚酸盐抑制血小板微泡的促泡沫细胞生成作用机制研究

Traditional Chinese medicine for promoting blood circulation and removing blood stasis has a significant improvement effect on the formation of atherosclerotic plaque in patients with coronary heart disease, but the mechanism of action has not been fully revealed. Salvia miltiorrhiza has always been regarded as a good medicine for “blood and blood circulation”. The main active ingredient, salvia miltiorrhiza polyphenolate, has been widely used in clinical practice. The applicant's previous study found that the anti-atherosclerosis effect of salvianolate was closely related to the formation process of foam cells, and suggested that "danshen polyphenolate may affect the interaction between platelet microbubbles and macrophages." The hypothesis of the generation of foam cells. In order to verify the scientific hypothesis and to further explore the mechanism of action of "blood-activating blood" drugs, this study intends to develop the effect of platelet microbubbles on foam cell production ability before and after treatment with salvia miltiorrhiza polymorphine macrophages, and synchronous detection of foam cell production. Target protein expression; look for significant differential proteins and use gene knockout techniques to reverse-recognize the importance of related proteins. In addition, this study will also construct a mouse model of atherosclerosis, and verify the conclusions of in vitro studies at the animal level. The above studies are expected to reveal the interaction between salvianolate and platelet-macrophages and its mechanism, and provide a scientific basis for the clinical application of salvianolate in the field of coronary heart disease.

中医药活血化瘀法对冠心病患者动脉粥样硬化斑块的形成有显著的改善效果，但作用机制尚未完全揭示。丹参历来被视为“活血行血”之良药，主要活性成分丹参多酚酸盐已在临床广泛应用。申请人前期研究发现丹参多酚酸盐的抗动脉粥样硬化作用与泡沫细胞的生成过程密切相关，进而提出“丹参多酚酸盐可能通过调控血小板微泡-巨噬细胞间的相互作用进而影响泡沫细胞的生成”这一假说。为验证该科学假说，同时深入探讨“活血行血”药物的作用机制，本研究拟开展丹参多酚酸盐作用巨噬细胞前后血小板微泡对泡沫细胞生成能力的影响，同步检测泡沫细胞生成相关靶蛋白的表达；寻找显著差异性蛋白并使用基因敲除等技术对相关蛋白的重要性进行反向确认。此外，本研究还将构建动脉粥样硬化小鼠模型，动物层面验证体外研究相关结论。上述研究有望揭示丹参多酚酸盐与血小板-巨噬细胞间的相互作用及其机制，进而为丹参多酚酸盐在冠心病相关领域的临床应用提供科学依据。

中医药活血化瘀法对冠心病患者动脉粥样硬化斑块的形成有显著的改善效果，但作用机制尚未完全揭示。丹参是植物活血药的代表，各种剂型的丹参也是目前心血管疾病临床应用和疗效证据最多的药物。本项目研究发现血小板来源的微泡能够促进泡沫细胞的生成，通过流式细胞学分析发现丹参多酚酸盐的预处理能够减轻泡沫细胞的生成能力，提示了丹参多酚酸盐的抗动脉粥样硬化作用。同时也发现丹参多酚酸盐能够减少巨噬细胞在受到刺激后炎症因子的分泌，提示了丹参多酚酸盐的抗炎作用。利用蛋白印迹等方法同时发现了可能的作用通路。同时课题组还探索了中性粒细胞诱捕网的重要成分cfDNA对于动脉粥样硬化的预测作用，利用当前人工智能中目前学术界应用最广泛的机器学习方法结合生化指标对冠状动脉狭窄进一步提高预测的准确率，同时申请了专利。相关成果获得了中国中西医结合学会心血管病专业委员会2020年度科学技术一等奖。这些研究成果，有望对更深入理解丹参这一祖国传统中药治疗心血管疾病背后的分子生物学机制，同时对动脉粥样硬化的诊疗手段提供了新的证据和思路。