Astragalus polysaccharides reduce high-glucose-induced rat aortic endothelial cell senescence and inflammasome activation by modulating the mitochondrial Na+/Ca2+ exchanger
Astragalus polysaccharides reduce high-glucose-induced rat aortic endothelial cell senescence and inflammasome activation by modulating the mitochondrial Na+/Ca2+ exchanger
复制标题
黄芪多糖通过调节线粒体Na/Ca2交换体减少高糖诱导的大鼠主动脉内皮细胞衰老和炎症小体活化
DOI：
10.1007/s12013-021-01058-w
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发表时间：
2021
影响因子：
2.6
通讯作者：
Chun-Lin Li
中科院分区：
文献类型：
--
作者：
Xin-Yu Miao;Xiao-Xiao Zhu;Zhao-Yan Gu;Bo Fu;Shao-Yuan Cui;Yuan Zu;Ling-Jun Rong;Fan Hu;Xiang-Mei Chen;Yan-Ping Gong;Chun-Lin Li
血管内皮细胞在老年人动脉粥样硬化的改变和心血管疾病的进展中起着至关重要的作用。以往的研究表明，黄芪多糖(APS)是中药黄芪的主要活性成分，在小鼠肝脏和脑中具有保护线粒体和延缓衰老的作用。然而，APS对大鼠主动脉内皮细胞(RAEC)衰老的影响及其机制尚未见报道。本研究采用组织块法从2月龄雄性Wistar大鼠肾小管上皮细胞中提取血管内皮细胞，发现黄芪多糖可改善高糖诱导的SA-β-Gal阳性细胞表达频率和衰老相关蛋白p16、p21和p53的表达水平。APS可提高高糖条件下培养的RAECs的成管能力。此外，APS可促进线粒体Na+/Ca~(2+)交换器NCLX的表达，而小干扰RNA(SiRNA)抑制NCLX的表达可抑制APS在高糖条件下的抗衰老作用。此外，黄连多糖可改善血管内皮细胞线粒体功能障碍，包括增加线粒体三磷酸腺苷产量、细胞色素C氧化酶活性和氧耗率，并抑制高糖诱导的NLRP3炎性小体激活和IL-1β的释放，而siNCLX可逆转这一作用。这些结果表明，黄芪多糖通过调节NCLX，减轻高糖诱导的炎性小体激活，改善线粒体功能障碍和衰老。此外，APS还增加了自噬相关蛋白(LC3B-II/I、ATG7)的水平，并增加了高糖条件下自噬空泡的数量。因此，这些数据表明APS可能通过NCLX减轻血管内皮细胞的炎症和衰老。
Vascular endothelial cells play a vital role in atherosclerotic changes and the progression of cardiovascular disease in older adults. Previous studies have indicated thatAstragaluspolysaccharides (APS), a main active component of the traditional Chinese medicineAstragalus, 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.