Astragaloside Ⅳ Alleviates the Effects of Hypoxia on Brain Microvascular Endothelial Cells Apoptosis and Inflammation by Down-Regulating miR-327
LIU Dan1, YU Guang-zhou2, SONG Jing-gui1*
1. Department of Neurology, Zhumadian Central Hospital, Zhumadian 463000, China; 2. Department of Neurology, the Second Affiliated Hospital of Xinxiang Medical College, Xinxiang 453000, China
Abstract：OBJECTIVE To explore the effect of astragaloside Ⅳ on the damage of brain microvascular endothelial cells(BMECs) treated with hypoxia and its molecular mechanism. METHODS BMECs were cultured in vitro and divided into control group, model group, low, medium and high dose astragaloside Ⅳ groups, high dose astragaloside Ⅳ+miR-NC group, and high dose astragaloside Ⅳ+miR-327 group. The tetramethylazozolate colorimetric method (MTT) was used to detect cell activity. Flow cytometry was used to detect cell apoptosis. Western blot was used to detect protein expression. The kits detected damage markers of BMECs, including lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). ELISA was used to evaluate the levels of interleukin-6 (IL-6), interleukin-1β(IL-1β) and tumor necrosis factor-α (TNF-α). Real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the expression of circDONSON. RESULTS Compared with the control group, the survival rate of BMECs decreased significantly at 9 h and 12 h after hypoxia treatment(P<0.05). Compared with the control group, the apoptosis rate of the model group was significantly increased, Bcl-2 expression level was significantly decreased, and Bax expression level was significantly increased (P<0.05). Compared with the model group, the apoptosis rates of the low, medium and high dose astragaloside Ⅳ groups were significantly reduced, the expression level of Bcl-2 was increased, and the expression level of Bax was decreased in a dose-dependent manner(P<0.05).Compared with the control group, LDH, MDA, IL-6, IL-1β and TNF-α expression levels in the model group were significantly increased, while SOD and GSH-PX expression levels were significantly decreased (P<0.05). Compared with the model group, the expression levels of LDH, MDA, IL-6, IL-1β and TNF-α in the low, medium and high dose astragaloside Ⅳ groups were significantly decreased, and the expression levels of SOD and GSH-PX were significantly increased in a dose-dependent manner(P<0.05). Compared with the control group, miR-327 expression level in the model group was significantly increased(P<0.05). Compared with the model group, the expression level of miR-327 in the low, medium and high dose astragaloside Ⅳ groups was significantly reduced dose-dependently(P<0.05). The overexpression of miR-327 reversed the effects of astragaloside Ⅳ on the apoptosis and inflammatory response of hypoxia treated BMECs. CONCLUSION Astragaloside Ⅳ may alleviate the effects of hypoxia on BMECs apoptosis and inflammation by down-regulating the expression of miR-327.
刘丹, 于广周, 宋景贵. 黄芪甲苷通过下调miR-327缓解缺氧对脑微血管内皮细胞凋亡及炎症反应的影响[J]. 中国药学杂志, 2021, 56(19): 1571-1576.
LIU Dan, YU Guang-zhou, SONG Jing-gui. Astragaloside Ⅳ Alleviates the Effects of Hypoxia on Brain Microvascular Endothelial Cells Apoptosis and Inflammation by Down-Regulating miR-327. Chinese Pharmaceutical Journal, 2021, 56(19): 1571-1576.
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2021, Vol. 56 
