Miao Xin-Yu, Zhu Xiao-Xiao, Gu Zhao-Yan, Fu Bo, Cui Shao-Yuan, Zu Yuan, Rong Ling-Jun, Hu Fan, Chen Xiang-Mei, Gong Yan-Ping, Li Chun-Lin
Department of Endocrinology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China.
Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.
Cell Biochem Biophys. 2022 Jun;80(2):341-353. doi: 10.1007/s12013-021-01058-w. Epub 2022 Feb 2.
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/Ca 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动脉粥样硬化改变和心血管疾病进展中起着至关重要的作用。先前的研究表明，黄芪多糖（APS）是中药黄芪的主要活性成分，可保护线粒体并在小鼠肝脏和大脑中发挥抗衰老作用。然而，APS对大鼠主动脉内皮细胞（RAEC）衰老的影响及其潜在机制尚未得到研究。在本研究中，我们采用组织块培养法从2月龄雄性Wistar大鼠中提取RAEC，发现APS可改善高糖诱导的SA-β-Gal阳性频率增加以及衰老相关蛋白p16、p21和p53的水平。APS增加了高糖条件下RAEC的管腔形成能力。此外，APS增强了线粒体钠/钙交换体NCLX的表达，通过小干扰RNA（siRNA）转染敲低NCLX可抑制高糖条件下APS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生成、细胞色素C氧化酶活性和氧消耗率（OCR），并抑制高糖诱导的NLRP3炎性小体激活和IL-1β释放，而siNCLX可逆转这些作用。这些结果表明，APS通过调节NCLX减少高糖诱导的炎性小体激活，改善RAEC的线粒体功能障碍和衰老。此外，APS在高糖条件下增强了自噬相关蛋白（LC3B-II/I、Atg7）的水平并增加了自噬泡的数量。因此，这些数据表明APS可能通过NCLX减少血管内皮细胞炎症和衰老。
