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基于“心合小肠”理论探讨肠道微生物对痰瘀互结证ACS血小板高反应性的影响及机制

批准号:
82104841
项目类别:
青年科学基金项目(C类)
资助金额:
30.0 万元
负责人:
张妮
依托单位:
学科分类:
中医内科学
结题年份:
2024
批准年份:
2021
项目状态:
已结题
项目参与者:
张妮

项目摘要

结项摘要

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中文摘要
ACS是我国发病率、死亡率、复发率均较高的疾病。抗栓治疗贯穿ACS始终,是防治ACS的基石。我国ACS患者HPR发生率高,规范化抗血小板治疗无法充分抑制血小板活性。肠道微生物组作为人体第二基因组,能够调节TMAO的生成直接影响HPR,是防治ACS的潜在靶点。《黄帝内经》“心合小肠,小肠者,脉其应”。小肠“泌别清浊”以养其心,小肠“主液”滑利血脉,小肠失于“别浊”化生痰瘀,痹阻心脉而为胸痹。在中医理论指导下,本课题拟以痰瘀互结证ACS患者及急性心肌缺血大鼠为研究对象,以肠道微生物菌群依赖性生物标志物TMAO为切入点,TMA/FMO3/TMAO信号通路为关键途径,血小板功能为关键环节,阐明痰瘀互结证ACS患者肠道微生物调控血小板功能的关键途径,并探讨化瘀祛痰方的干预作用及机制,丰富中医“心合小肠”理论科学内涵,为挖掘以肠道微生物组为有效靶点防治心血管疾病中药复方提供新的研究策略和科学依据。
英文摘要
ACS is a disease with high morbidity, mortality, and recurrence rate in my country. Antithrombotic therapy runs through ACS and is the cornerstone of prevention and treatment of ACS. The incidence of HPR in ACS patients in my country is high, and standardized antiplatelet therapy cannot fully inhibit platelet activity. As the second human genome, the gut microbiome can regulate the production of TMAO and directly affect HPR, and is a potential target for the prevention and treatment of ACS. “Huangdi Neijing” said that “the heart is in harmony with the small intestine, and the pulse is its reflection.” The small intestine “secrets the clear and turbidity” to nourish the heart, the small intestine “directing fluid” smoothes the blood vessels, the small intestine loses the “secret turbidity” to transform phlegm and blood stasis, block the heart pulse and become chest numbness. Under the guidance of TCM theory, the subject is planning to take ACS patients with phlegm and blood stasis syndrome and acute myocardial ischemia rats as the research objects, the gut microbes-dependent biomarker TMAO as the entry point, the TMA/FMO3/TMAO signaling pathway as the key pathway, and the platelet Function as the key link, to clarify the key ways of gut microbiome regulating platelet function in ACS patients with phlegm and blood stasis syndrome, and explore the interventional effect and mechanism of Huayu Qutan Recipe, enrich the scientific connotation of the theory of “the heart is in harmony with the small intestine” in TCM, provide new research strategies and scientific basis for the discovery of the gut microbiome as an effective target for the prevention and treatment of cardiovascular diseases.
ACS是我国发病率、死亡率、复发率均较高的疾病。抗栓治疗贯穿ACS始终,是防治ACS的基石。我国ACS患者HPR发生率高,规范化抗血小板治疗无法充分抑制血小板活性。肠道微生物组作为人体第二基因组,能够调节TMAO的生成直接影响HPR,是防治ACS的潜在靶点。《黄帝内经》“心合小肠,小肠者,脉其应”。小肠“泌别清浊”以养其心,小肠“主液”滑利血脉,小肠失于“别浊”化生痰瘀,痹阻心脉而为胸痹。在中医理论指导下,本项目以痰瘀互结证ACS患者及急性心肌缺血大鼠为研究对象,阐明其肠道微生物组特征,探讨肠道微生物驱动TMA/FMO3/TMAO信号通路对血小板功能的影响,及化瘀祛痰方的干预作用及机制。研究通过临床试验及动物实验发现,肠道微生物在ACS的发生和发展中具有潜在的预测作用,包括但不限于主要的菌门厚壁菌门、拟杆菌门、放线菌门和变形菌门,也包括一些低丰度的菌门梭杆菌门、疣微菌门、螺旋体门和去铁菌门。菌群森林的变化可驱动TMA/FMO3/TMAO通路促进血小板聚集。化瘀祛痰方可通过调节肠道微生物驱动TMA/FMO3/TMAO通路调节肠道菌群功能,改善血小板聚集,从而预防ACS。目前化瘀祛痰方已为我院院内制剂,本研究为该制剂的临床应用提供了科研数据,并为扩大适应症奠定了一定的基础。且研究发现Akkermansia可能是一种有前景的益生菌,可驱动TMA/FMO3/TMAO通路调节花生四烯酸代谢,从而改善血小板聚集,有望成为临床抗血小板聚集的新靶点。本研究结果为“心与小肠相连”理论提供了理论依据。
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