Department of Histology and Embryology, School of Basic Medicine, Central South University, Changsha, Hunan, China (mainland).
Department of Anatomy, Histology, and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha, Hunan, China (mainland).
Med Sci Monit. 2019 Jul 10;25:5127-5136. doi: 10.12659/MSM.916287.
BACKGROUND Aging plays an important role in endothelial dysfunction. Fluid shear stress (FSS) can activate endothelial cells (ECs). Herein, we tested the hypothesis that this endothelial impairment could be improved by elevated FSS (EFSS) in aged rats. MATERIAL AND METHODS EFSS was created through ligation of the unilateral common iliac artery in 20-month-old rats, evaluated by measuring blood flow velocity with Doppler spectrum. The effect of FSS on aged ECs was examined by senescence-associated ß-galactosidase (SA-ß-Gal) staining, ultrastructural observation, and immunostaining and qPCR analysis of eNOS and SIRT1 expression on both the mRNA and protein levels. RESULTS (1) FSS was significantly increased in the right common iliac artery (RCIA) in rats with the ligation of the left common iliac artery (LCIA). (2) SA-ß-Gal staining was significantly attenuated by EFSS in the RCIA of aged rats. (3) Ultrastructural observation showed that ECs in the RCIA of normal aged rats became irregular and enlarged, with increasingly polypoid nuclei and fewer mitochondria, whereas ECs in the RCIA of aged rats with LCIA ligation became more prominent and contained more mitochondria. (4) eNOS and SIRT1 expression in the RCIA of aged rats with LCIA ligation was significantly upregulated compared with that in control group rats. CONCLUSIONS The present study for the first time shows that EFSS has the ability to improve age-related impairment of endothelial structure and functions.
衰老是内皮功能障碍的重要因素。流体切应力(FSS)可以激活内皮细胞(ECs)。在此,我们通过结扎 20 月龄大鼠单侧髂总动脉,用多普勒频谱测量血流速度来验证这一假说,即升高的 FSS(EFSS)可改善老年大鼠的内皮损伤。
EFSS 通过结扎左侧髂总动脉来创建,通过多普勒频谱测量血流速度来评估。通过衰老相关β-半乳糖苷酶(SA-ß-Gal)染色、超微结构观察以及 eNOS 和 SIRT1 表达的免疫染色和 qPCR 分析,检测 FSS 对老年 ECs 的影响,检测的指标包括 mRNA 和蛋白水平。
(1)结扎左侧髂总动脉后,右侧髂总动脉(RCIA)中的 FSS 显著增加。(2)EFSS 可显著减弱衰老大鼠 RCIA 中的 SA-ß-Gal 染色。(3)超微结构观察表明,正常衰老大鼠 RCIA 中的 ECs 变得不规则且增大,核呈息肉样,线粒体越来越少,而结扎左侧髂总动脉后衰老大鼠 RCIA 中的 ECs 则变得更加突出,并且含有更多的线粒体。(4)与对照组大鼠相比,结扎左侧髂总动脉后衰老大鼠 RCIA 中的 eNOS 和 SIRT1 表达显著上调。
本研究首次表明,EFSS 具有改善与年龄相关的内皮结构和功能损伤的能力。