CXCL9介导的炎症与免疫调控在血管衰老中的研究进展

Research Advances on CXCL9-Mediated Inflammatory and Immune Regulation in Vascular Aging

摘要: 血管衰老是老年心血管疾病发生发展的关键病理基础，其核心驱动机制涉及慢性低度炎症与免疫稳态失衡。CXCL9作为一种受干扰素-γ (IFN-γ)调控的CXC亚家族趋化因子，近年来被证实为连接炎症启动与免疫定向浸润的关键分子节点。本文系统综述CXCL9的生物学特性及其在血管衰老进程中的调控作用与临床意义。CXCL9通过与其特异性受体CXCR3结合，激活下游PI3K-Akt、MAPK及NF-κB等多条信号通路，介导炎症信号放大与细胞功能紊乱。在衰老过程中，血管组织内CXCL9呈异常高表达：一方面通过放大促炎信号、抑制抗炎反应及诱发内皮功能障碍，加剧局部炎症微环境紊乱；另一方面通过特异性招募并激活Th1细胞、巨噬细胞等促炎性免疫细胞，形成正反馈级联环路，破坏M1/M2及Th1/Th2免疫平衡，从而驱动血管壁结构与功能的退行性重塑。临床研究表明，CXCL9在动脉粥样硬化、高血压及血管源性认知障碍等多种老年血管疾病中表达上调，其表达水平与血管僵硬度、内皮功能损伤程度及不良预后显著相关，提示其作为潜在诊断标志物与干预靶点的临床应用价值。本文亦系统梳理当前研究的局限性，并从分子机制深入解析、临床转化路径探索及靶向干预策略开发等方向进行展望，以期为深入理解血管衰老的免疫调控机制及研发相关防治新策略提供理论依据。

Abstract: Vascular aging is a critical pathological basis for the onset and progression of age-related cardiovascular diseases, with its core driving mechanisms involving chronic low-grade inflammation and immune homeostasis imbalance. CXCL9, a CXC subfamily chemokine regulated by interferon-gamma (IFN-γ), has recently been identified as a key molecular node linking inflammatory initiation and directed immune infiltration. This article systematically reviews the biological characteristics of CXCL9 and its regulatory role and clinical significance in vascular aging. By binding to its specific receptor CXCR3, CXCL9 activates downstream signaling pathways, such as PI3K-Akt, MAPK, and NF-κB, mediating inflammatory signal amplification and cellular dysfunction. During aging, CXCL9 is abnormally upregulated in vascular tissues: on one hand, it exacerbates local inflammatory microenvironment disturbances by amplifying pro-inflammatory signals, suppressing anti-inflammatory responses, and inducing endothelial dysfunction; on the other hand, it specifically recruits and activates pro-inflammatory immune cells, such as Th1 cells and macrophages, forming a positive feedback cascade that disrupts M1/M2 and Th1/Th2 immune balance, thereby driving degenerative remodeling of vascular structure and function. Clinical studies have shown that CXCL9 expression is upregulated in various age-related vascular diseases, including atherosclerosis, hypertension, and vascular cognitive impairment, and its expression levels are significantly correlated with vascular stiffness, degree of endothelial dysfunction, and poor prognosis, suggesting its potential clinical value as a diagnostic biomarker and therapeutic target. This article also systematically summarizes the limitations of current research and provides perspectives on future directions, including in-depth exploration of molecular mechanisms, clinical translation pathways, and development of targeted intervention strategies, aiming to provide a theoretical basis for further understanding the immune regulatory mechanisms of vascular aging and for developing novel preventive and therapeutic approaches.