基于“力学-生物信号”通路Integrin-YAP/TAZ-JNK探讨理气活血滴丸对动脉粥样硬化血管稳态的作用及机制

动脉粥样硬化(atherosclerosis, As)是导致心脑血管疾病的主要病理基础，血管功能和结构的稳态平衡(血管稳态)是多机制复合的结果，是血管疾病的关键病理环节。研究证明不同的血流剪切力可通过调节血管内皮细胞功能影响血管稳态。新近研究表明AS与“生物-力学信号”通路Integrin--YAP/TAZ-JNK调节密切相关。本课题组所在单位前期研究表明理气活血滴丸对冠心病疗效确切，有改善血流动力学，有活血化瘀、抗血小板聚集及抑制血栓形成作用。为此，我们拟通过运用临床疗效确切的成药制剂理气活血滴丸（米槁心乐滴丸），基于“力学-生物信号”复杂通路“整合素-YAP/TAZ-JNK信号”，从细胞和动物水平验证理气活血滴丸干预AS发生、维持进程中血管稳态与关键信号通路的分子调控机制，明确治疗靶点，探索理气活血滴丸多靶点起效的靶点网络，系统的分析其药效作用机制，进一步探讨中药抗动脉粥样硬化的作用。

Atherosclerosis is the main pathological basis of cardiovascular and cerebrovascular diseases. The steady state balance of vascular function and structure (vascular homeostasis) is the result of multiple mechanisms and is the key pathological part of vascular disease. Existing studies have demonstrated that different blood flow shear forces can affect vascular homeostasis by regulating vascular endothelial cell function. Recent studies have shown that AS is closely related to the regulation of the "bio-mechanical signal" pathway Integrin--YAP/TAZ-JNK. The previous research of the unit of the research group showed that Liqi Huoxue Pill is effective in treating coronary heart disease, improving hemodynamics, promoting blood circulation, preventing platelet aggregation and inhibiting thrombosis. To this end, we intend to use the clinically effective pharmaceutical preparations of Liqi Huoxue Dropping Pills (Miqi Xinle Drop Pills), based on the "mechanical-biological signal" complex pathway "integrin-YAP/TAZ-JNK signal", from cells and Animal level verification Liqi Huoxue Drop Pill interferes with the molecular regulation mechanism of vascular homeostasis and key signaling pathways in AS development and maintenance process, clarifies therapeutic targets, explores the target network of Liqi Huoxue Dropping Pills, and systematically analyzes its target network. The mechanism of pharmacodynamic action further explores the mechanism of action of traditional Chinese medicine against atherosclerosis.