益气活血中药通过巨噬细胞Cx43调控其代谢重编程抗动脉硬化的作用与机制研究

最新研究发现，巨噬细胞（M ø ）在斑块微环境下发生的代谢重编程-糖酵解是调控其极化表型，促炎、促AS的重要机制。Cx43是其主要连接蛋白，可在细胞间传递葡萄糖分子，实现代谢偶联，抑制其表达具有抗AS作用。但能否影响M ø代谢方向和功能表型尚不明确。我们前期发现益气活血具有上调内皮细胞Cx43表达，促新生血管成熟作用，并可抑制M ø Cx43表达及葡萄糖转运。于是提出假说：益气活血中药通过抑制M ø Cx43表达，调控同一微环境下M ø群的代谢方向及功能表型，而实现抗AS。本课题构建AS动物模型，采用qRT-PCR、W-B、流式分选、质粒或siRNA转染及代谢组学分析等技术，研究益气活血中药的抗AS作用及对斑块局部mø功能表型、代谢状态的影响，以及改变巨噬细胞Cx43后其功能表型、代谢状态的变化。创新性地从巨噬细胞Cx43与代谢调控角度拓展益气活血中药防治AS的作用机理并提供新的防治依据。

Recent studies have found that metabolic reprogramming of macrophages (m ø) -glycolysis in plaque microenvironment is an important mechanism to regulate its polarized phenotype, promote inflammation and promote AS. Cx43 is the main connexin, which can transfer glucose molecules between cells, realize metabolic coupling, inhibit its expression and have anti as effect. However, it is not clear whether the metabolic direction and functional phenotype of macrophages can be influenced by sharing metabolic molecules. We found that Yiqi Huoxue Chinese medicine has the effect of anti-AS, it can up regulate the expression of Cx43 in endothelial cells, promote the maturation of neovascularization, and it also can inhibit the Cx43 expression of macrophages and glucose transport. Therefore, the hypothesis is put forward: Yiqi Huoxue Chinese medicine can achieve the anti-AS effect by inhibiting m ø Cx43, changing its microenvironment and regulating the glycolysis. In this study, the animal model of AS was constructed. QRT-PCR, W-B, flow separation, plasmid or siRNA transfection and metabonomics analysis were used to study the anti-AS effect of Yiqi Huoxue Chinese medicine and its influence on the functional phenotype and metabolic state of M Φ in plaque, and the change of functional phenotype and metabolic state of macrophage after changing Cx43. From the point of view of macrophage Cx43 and metabolic regulation, the new mechanism of Yiqi Huoxue Chinese medicine in the prevention and treatment of AS was expanded, providing a new scientific basis for Yiqi Huoxue Chinese medicine in the prevention and treatment of as related diseases