Vascular endothelial cells play a vital role in atherosclerotic changes and the progression of cardiovascular disease in older adults. Previous studies have indicated that Astragalus polysaccharides (APS), a main active component of the traditional Chinese medicine Astragalus, protect mitochondria and exert an antiaging effect in the mouse liver and brain. However, the effect of APS on rat aortic endothelial cell (RAEC) senescence and its underlying mechanism have not been investigated. In this study, we extracted RAECs from 2-month-old male Wistar rats by the tissue explant method and found that APS ameliorated the high-glucose-induced increase in the frequency of SA-β-Gal positivity and the levels of the senescence-related proteins p16, p21, and p53. APS increased the tube formation capacity of RAECs under high-glucose conditions. Moreover, APS enhanced the expression of the mitochondrial Na⁺/Ca²⁺ exchanger NCLX, and knockdown of NCLX by small interfering RNA (siRNA) transfection suppressed the antiaging effect of APS under high-glucose conditions. Additionally, APS ameliorated RAEC mitochondrial dysfunction, including increasing ATP production, cytochrome C oxidase activity and the oxygen consumption rate (OCR), and inhibited high-glucose-induced NLRP3 inflammasome activation and IL-1β release, which were reversed by siNCLX. These results indicate that APS reduces high-glucose-induced inflammasome activation and ameliorates mitochondrial dysfunction and senescence in RAECs by modulating NCLX. Additionally, APS enhanced the levels of autophagy-related proteins (LC3B-II/I, Atg7) and increased the quantity of autophagic vacuoles under high-glucose conditions. Therefore, these data demonstrate that APS may reduce vascular endothelial cell inflammation and senescence through NCLX.

血管内皮细胞在老年人的动脉粥样硬化变化和心血管疾病的进展中起着至关重要的作用。以往研究表明，中药黄芪的主要活性成分黄芪多糖（APS），保护线粒体并在小鼠肝脏和大脑中发挥抗衰老作用。然而，尚未研究 APS 对大鼠主动脉内皮细胞 (RAEC) 衰老的影响及其潜在机制。在本研究中，我们通过组织移植法从 2 个月大的雄性 Wistar 大鼠中提取 RAEC，发现 APS 改善了高糖诱导的 SA-β-Gal 阳性频率和衰老水平的增加。相关蛋白 p16、p21 和 p53。APS 增加了高糖条件下 RAEC 的管形成能力。此外，APS 增强了线粒体 Na ⁺ /Ca ^2+的表达交换器 NCLX 和通过小干扰 RNA (siRNA) 转染敲低 NCLX 可抑制 APS 在高葡萄糖条件下的抗衰老作用。此外，APS 改善了 RAEC 线粒体功能障碍，包括增加 ATP 产生、细胞色素 C 氧化酶活性和耗氧率 (OCR)，并抑制高糖诱导的 NLRP3 炎性体活化和 IL-1β 释放，而这些被 siNCLX 逆转。这些结果表明，APS 通过调节 NCLX 减少了高葡萄糖诱导的炎症小体活化并改善了 RAEC 中的线粒体功能障碍和衰老。此外，APS 提高了自噬相关蛋白（LC3B-II/I、Atg7）的水平，并在高糖条件下增加了自噬泡的数量。所以，