心血管疾病是全球死亡和致残的首要原因，现有标准治疗虽能降低急性事件风险，但“残余风险”依然显著，亟需多靶点干预策略。延胡索乙素（tetrahydropalmatine，THP）作为延胡索生物碱中的主要活性成分，具有独特的四环骨架结构和多靶点药理特性，在心律失常、血小板过度聚集与血栓形成、高血压及内皮功能障碍、心室重塑等关键病理环节均发挥显著作用，其机制涉及多离子通道协同调控、一氧化氮合成与内皮依赖性舒张增强、交感神经活性抑制、纤维化及肥厚抑制等。此外，THP还可通过激活磷脂酰肌醇3-激酶/蛋白激酶B通路等保护性通路，抑制丝裂原活化蛋白激酶通路、核因子κB通路等致病性通路，从而发挥抗炎、抗凋亡、抗氧化及促血管新生等综合效应。然而，THP仍存在口服生物利用度有限、体内代谢途径复杂以及临床循证研究不足等关键障碍。因此，本综述系统梳理了THP在心血管疾病中的药理作用及分子机制，旨在揭示其多靶点、多通路的潜在价值，并为后续药动学优化、制剂改良及临床研究提供理论依据。

Cardiovascular diseases are the leading cause of death and disability worldwide. Although existing standard therapies can reduce the risk of acute events, a significant “residual risk” remains, highlighting the urgent need for multi-target intervention strategies. Tetrahydropalmatine (THP), the principal active alkaloid in Corydalis yanhusuo, features a unique tetracyclic scaffold and exhibits multitarget pharmacological characteristics. It plays significant roles in key pathological processes, including arrhythmia, platelet hyperaggregation and thrombosis, hypertension and endothelial dysfunction, and ventricular remodeling. Its mechanisms involve the coordinated regulation of multiple ion channels, enhancement of nitric oxide synthesis and endothelium-dependent relaxation, suppression of sympathetic nerve activity, and inhibition of fibrosis and hypertrophy. Furthermore, THP can activate protective signaling pathways such as the phosphatidylinositol 3-kinase/protein kinase B pathway, while inhibiting pathogenic pathways including the mitogen-activated protein kinase and nuclear factor-κB pathways, thereby exerting comprehensive effects such as anti-inflammatory, anti-apoptotic, antioxidant, and pro-angiogenic actions. However, THP still faces critical limitations, including low oral bioavailability, complex metabolic pathways, and insufficient clinical evidence. Therefore, this review systematically summarizes the pharmacological effects and molecular mechanisms of THP in cardiovascular diseases, aiming to elucidate its potential value as a multi-target and multi-pathway therapeutic agent, and to provide a theoretical foundation for further pharmacokinetic optimization, formulation improvement, and clinical investigation.

R285

河北省医学科学研究课题（20230608）