巨噬细胞介导的免疫炎症反应在高血压血管外膜重塑中发挥重要作用。NOD-like Receptor 3 (NLRP3)是主要存在于巨噬细胞中的免疫感受和激活信号通路，通过半胱天冬酶-1-白介素途径参与炎症的调控。NLRP3炎症小体的激活多依赖于巨噬细胞线粒体稳态的失衡，但巨噬细胞是如何整合线粒体自由基和能量代谢，调节NLRP3炎症小体的活化，分泌促炎因子，启动免疫应答的机制尚不清楚。我们研究发现在自发性高血压动物模型中，血管外膜的损伤伴随NLRP3的激活和线粒体去乙酰化酶SIRT3表达的下降，推测巨噬细胞SIRT3的缺陷可能导致NLRP3的激活。本项目拟通过体内外实验研究，SIRT3调控巨噬细胞线粒体稳态的作用；SIRT3激活NLRP3炎症小体的作用；SIRT3在损伤外膜重构中的作用。阐明SIRT3-线粒体稳态-NLRP3炎症小体-外膜重塑之间的关系，为防治高血压的发生发展开辟新的思路。

Macrophage-mediated immune inflammatory response may play an important role in adventitial remodeling in hypertension. The Nod-like receptor (NLR) family, pyrin domain containing 3 (NLRP3) is critical for caspase-1 activation and the secretion of IL-1β in response to multiple microbial molecules and endogenous danger molecules. Dysfunctional mitochondria are emerging as the key feature leading to NLRP3 activation, but the exact nature of the NLRP3-activating mitochondrial signal is still unclear. In previous study, we found that NLRP3 inflammasome activitation was in accordance with decreased SIRT3 protein level and adventitial injury in spontaneously hypertensive rats. We presumed that SIRT3-deficient might be involved in NLRP3 activation. The aim of the study is to investigate: effects of SIRT3 on altertion of mitochondrial dynamic; effects of SIRT3 on NLRP3 activitation and effects of SIRT3 on adventitial remodeling. This work would clarify the relationship among SIRT3, mitochondrial homeostasis, NLRP3 activitation and adventitial remodeling. Activation of SIRT3 may be a promising target for the treatment of hypertension.