Effect of Apigenin on angiogenesis and neurogenesis in the cerebral ischemic penumbra of middle cerebral artery occlusion rat via VEGF signaling pathway
LIU Chan, HU Quan, XIE Qingfeng, ZHU Anqi, CHEN Xiang.
Department of Children Rehabilitation, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, China
LIU Chan,HU Quan,XIE Qingfeng, et al. Effect of Apigenin on angiogenesis and neurogenesis in the cerebral ischemic penumbra of middle cerebral artery occlusion rat via VEGF signaling pathway[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(3): 182-188.
Abstract：Objective: To investigate the effects of Apigenin (APG)-induced angiogenesis and neurogenesis in the cerebral ischemic penumbra of middle cerebral artery occlusion (MCAO) rats and whether these changes involve the vascular endothelial growth factor (VEGF) signaling pathway. Methods: A total of 144 adult male Sprague Dawley rats were randomly divided into sham operation group (groups S7 and S14, respectively), a model group (groups M7 and M14, respectively), an APG treatment model group (groups AM7 and AM14,respectively), and an APG+VEGF-R inhibitor treatment model group (groups AIM7 and AIM14, respectively).A MCAO animal model was established; neurobehavioral performance and infarct volumes were assessed using the modified neurological severity score (mNSS) and 2, 3, 5‑triphenyl tetrazolium chloride staining; VEGF expression levels, and changes in angiogenesis and new neurons in the cerebral ischemic penumbra were evaluated using Western blot analysis, immunohistochemistry, and immunofluorescence. Results: Compared with the S group, the neurologic impairment symptoms and white infarcts were observed in the M group, AM group and AIM group; the neurological scores and infarct volume in the AM group were significantly decreased compared with those in the M group at the same time-point (P<0.05). The VEGF expression in the AM group was increased compared with that in the M group at the same time-point (P<0.01), and microvessel density was increased in the AM7 group compared with that in the M7 group (P<0.05). The number of bromodeoxyuridine (BrdU)/nestin and BrdU/NeuN double-labeled positive cells in the AM group were significantly increased compared with those in the M group at the same time-point (P<0.01). VEGF-R inhibitors reversed the improvement effect of APG. Conclusion: APG ameliorates focal cerebral ischemia/reperfusion-induced neurological deficit by promoting angiogenesis and neurogenesis through upregulation of the VEGF signaling pathway.
