Ce Liang1, Guang-Xiao Ni2, Xu-Liang Shi3, Lin Jia4, Ya-Li Wang1,2. 1. Department of TCM Diagnostics, Hebei University of Chinese Medicine, Shijiazhuang, China. 2. Department of Teaching and Research Section of Integrative Medicine, Hebei Medical University, Shijiazhuang, China. 3. Department of Acupuncture and Moxibustion, Hebei University of Chinese Medicine, Shijiazhuang, China. 4. Department of Respiratory, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, China.
Abstract
BACKGROUND: Astragaloside IV (AS-IV) is one of the main active ingredients of Astragalusmembranaceus. Studies have shown that AS-IV stimulates angiogenesis, including cell proliferation, migration, and neovascularization. However, the relevant mechanism remains unclear. OBJECTIVE: This study aims to investigate whether AS-IV activates the HIF/VEGF/Notch signaling pathway through miRNA-210 to promote angiogenesisafter ischemic stroke. METHODS: The present study established a rat model of middle cerebral artery occlusion (MCAO) and cultured human umbilical vein endothelial cells (HUVECs) under hypoxic conditions in vitro to investigate the role of AS-IV in promoting angiogenesis and reveal its underlying mechanism. Through in vivo studies, the area of cerebral infarction was determined by 2,3,5-triPhenyltetrazolium chloride (TTC) staining. Immunofluorescence staining and RT-qPCR were used to detect the expression changes of miRNA-210 and ephrinA3 in the ischemic cortex after ischemia. Through in vitro studies, cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Subsequently, angiogenesis experiments were performed to observe the angiogenic ability. RESULTS: Results revealed that AS-IV significantly reduced infarct size, promoted cell proliferation and ductal formation, and inhibited the expression of the target gene ephrinA3 by increasing the expression of miRNA-210 and inducing activation of the HIF-VEGF-Notch signaling pathway. CONCLUSIONS: AS-IV promotes cerebral protection following angiogenesis and ischemic brain injury. The specific mechanism was activating the HIF/VEGF/Notch signaling pathway via miRNA-210.
BACKGROUND:Astragaloside IV (AS-IV) is one of the main active ingredients of Astragalusmembranaceus. Studies have shown that AS-IV stimulates angiogenesis, including cell proliferation, migration, and neovascularization. However, the relevant mechanism remains unclear. OBJECTIVE: This study aims to investigate whether AS-IV activates the HIF/VEGF/Notch signaling pathway through miRNA-210 to promote angiogenesisafter ischemic stroke. METHODS: The present study established a rat model of middle cerebral artery occlusion (MCAO) and cultured human umbilical vein endothelial cells (HUVECs) under hypoxic conditions in vitro to investigate the role of AS-IV in promoting angiogenesis and reveal its underlying mechanism. Through in vivo studies, the area of cerebral infarction was determined by 2,3,5-triPhenyltetrazolium chloride (TTC) staining. Immunofluorescence staining and RT-qPCR were used to detect the expression changes of miRNA-210 and ephrinA3 in the ischemic cortex after ischemia. Through in vitro studies, cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Subsequently, angiogenesis experiments were performed to observe the angiogenic ability. RESULTS: Results revealed that AS-IV significantly reduced infarct size, promoted cell proliferation and ductal formation, and inhibited the expression of the target gene ephrinA3 by increasing the expression of miRNA-210 and inducing activation of the HIF-VEGF-Notch signaling pathway. CONCLUSIONS: AS-IV promotes cerebral protection following angiogenesis and ischemic brain injury. The specific mechanism was activating the HIF/VEGF/Notch signaling pathway via miRNA-210.