黄芪多糖通过线粒体钠钙交换蛋白调节自噬与炎症延缓内皮细胞衰老的机制研究

内皮细胞功能紊乱是血管衰老的启动因素，预防血管内皮损伤可延缓动脉粥样硬化的发生、发展。我们克隆到一种在主动脉内皮细胞中高表达的新型钠钙交换蛋白NCEX（NCLX），发现NCLX通过调节线粒体功能，抑制自噬、炎症和氧化应激反应，减少血管内皮细胞的损伤。前期研究示糖尿病大鼠主动脉内皮表达的NCLX可调节线粒体功能。高糖下调NCLX继而阻碍线粒体钙外排，呼吸链产生ROS增多，线粒体损伤积累，NLRP3炎性小体激活，诱发炎症瀑布反应。黄芪多糖治疗的糖尿病大鼠主动脉组织NCLX基因和蛋白表达均上调，主动脉粥样硬化病变减轻，提示黄芪多糖可能是通过NCLX途径发挥其对内皮细胞的保护作用。预实验显示黄芪多糖也可以上调自然衰老的内皮细胞NCLX的表达，调控自噬，延缓内皮细胞的衰老，但具体作用通路和关键因子尚不清楚，对该机制的探讨可深化对黄芪多糖作用机制的认识，有望为延缓血管衰老进程提供新的药物治疗靶点。

Endothelial dysfunction is the starting factor of vascular aging. Effectively preventing vascular endothelial injury can delay the occurrence and development of atherosclerosis. We cloned a new Na+/Ca2+ exchanger protein, NCEX ( NCLX ), which was highly expressed in aortic endothelial cells. NCLX inhibited autophagy, inflammation and oxidative stress reaction by adjusting mitochondrial function, thus reducing endothelial injury. Our previous studies showed that NCLX expressed in DM rat aortic endothelia regulated mitochondrial function. Suppression of NCLX expression induced by hyperglycemia blocked mitochondrial Ca2+ efflux, caused mitochondria function injury, increased ROS production, generated autophagy-related NLRP3 and inflammatory cascade. Astragalus polysaccharides (APS) upregulated the expression of NCLX gene and protein in DM rat aortic endothelia, and alleviated atherosclerotic lesion. It is suggested that APS play a protective role for endothelial cells, and its mechanism may be related to NCLX. Our preliminary experiments showed that APS upregulated NCLX expression in natural aging endothelial cells, regulated autophagy, and delayed the aging of endothelial cells. But the specific pathways and key factors remain unclear. To investigate the protective effect of APS on endothelial cells through NCLX-mediated autophagy and inflammatory response is expected to further clarify the function of astragalus polysaccharide and its mechanism. This study is also expected to find new safe and effective prevention and treatment of endothelial cell injury and early vasculopathy, and to provide theoretical basis for retarding vascular aging.