炎症损伤是血管衰老的重要诱因之一，趋化因子受体(CXCR)在动员免疫细胞介导的血管内皮细胞炎症损伤中发挥关键作用。我们前期发现，压力超负荷诱导表达CXCR6的单核-巨噬细胞在血管内皮浸润，加速内皮细胞损伤和老化，但在CXCR6基因敲除小鼠有明显改善，潜在分子机制不明确。本项目拟通过在体主动脉弓缩窄（TAC）模型和细胞接触共培养，研究CXCR6趋化的免疫细胞在诱导血管内皮细胞ROS水平、自噬功能紊乱，炎性小体NLRP3形成和信号通路激活中调控机制。检测jagged1、Sirt1、β-半乳糖苷酶等细胞衰老指标；通过干预免疫细胞浸润、氧化应激、自噬、构建ASC和caspase1腺相关病毒siRNA阻断NLRP3激活，评价NLRP3对血管老化的影响；以及CXCR6诱导血管内皮老化在NLRP3基因敲除小鼠是否逆转。明确CXCR6介导NLRP3通路在血管老化中分子机制，为血管内皮保护提供新的干预靶点。

Inflammatory injury is one of important causes of vascular senescence, and chemokine receptor CXCR6 plays a key role in mobilization of immune cells and vascular endothelial injury. Our previous study confirms that CXCR6 positive monocyte-macrophages infiltrate in vascular endothelium in response to pressure overload, which accelerates the injury and aging of the endothelial cells, but this phenomenon is not appeared in CXCR6 knockout mice. However, the potential mechanism is not clear. In the present study, we investigate the penitential role CXCR6-mediated immune cells in regulating ROS levels, autophagic dysfunction, and NLRP3 inflammasome formation in endothelial cells with the in vivo model of transverse aortic constriction (TAC) and the in vitro model of cell contact co-culture. We determine the alternation of jagged1, Sirt1 and β-galactosidase, and evaluate the effect of NLRP3 activation on vascular aging through suppressing immune cells infiltration, oxidative stress, autophagy, and NLRP3 inflammasome formation with AAV-expressing ASC siRNA and caspase1 siRNA. We also examine whether CXCR6-mediated senescence of endothelial cell can be reversed in NLRP3 gene knockout mice. Collectively, we aim to elucidate the mechanism of CXCR6-dependent NLRP3 signaling in vascular aging, which may shed a light on the new target for the vascular endothelial protection.