Abstract
Background: Ischemia stroke is known as the major cause of morbidity and mortality. Buyang Huanwu Decoction (BHD), a classical traditional Chinese medicine (TCM) formula, has been used to prevent and treat stoke for hundreds of years. The purpose of present study is to investigate the effects of BHD on angiogenesis in rats after cerebral ischemia/reperfusion (I/R) injury targeting Silent information regulator 1 (SIRT1) / Vascular endothelial growth factor (VEGF) pathway.Methods: The cerebral I/R injury model was induced by middle cerebral artery occlusion (MCAO). Adult Sprag-Dawley (SD) rats were randomly divided into five groups: sham group, normal saline (NS) group, BHD group, BHD+EX527 (SIRT1 specific inhibitor) group, and NS+EX527 group. Each group was divided into the subgroups according to 1, 3, 7, or 14 days time-point after cerebral ischemia/reperfusion, respectively. Neurological function score (NFS) was evaluated by the Rogers scale; microvascular density (MVD) in brain tissue around infarction area was observed by immunofluorescence; and the expression of SIRT1 and VEGF was assessed by Western Blot and Quantitative Real-time-PCR.Results: BHD can significantly improve NFS (P < 0.05), increase the MVD in the boundary ischemic area (P < 0.01) and elevate the expression of protein and mRNA of SIRT1 and VEGF following I/R injury (P < 0.01). In contrast, treatment with EX527 reversed the BHD-induced improvements in NFS (P < 0.01) and decreased the MVD (P < 0.01) and the expression of SIRT1 and VEGF (P < 0.05).Conclusion: BHD exerts neuroprotection targeting angiogenesis through the up-regulation of SIRT1/VEGF pathway against cerebral ischemic injury in rats.
Highlights
Stroke is characterized by acute disturbance of cerebral blood circulation, leading to long-term disability and death worldwide (GBD 2016 Causes of Death et al, 2017)
In normal saline (NS) group, Neurological function score (NFS) significantly decreased at 3 days after cerebral I/R when compared with that at 1 day (P < 0.05); NFS significantly decreased at 7 days when compared with 3 days (P < 0.05); NFS significantly decreased at 14 days when compared with 7 days (P < 0.05)
In Buyang Huanwu Decoction (BHD) group, NFS significantly decreased at 3 days when compared with 1 day (P < 0.05); NFS significantly decreased at 7 days when compared with 3 days (P < 0.05); NFS significantly decreased at 14 days when compared with 7 days (P < 0.05)
Summary
Stroke is characterized by acute disturbance of cerebral blood circulation, leading to long-term disability and death worldwide (GBD 2016 Causes of Death et al, 2017). Current treatments of ischemic stroke recommended by guidelines are mainly intravenous thrombolysis of tissue plasminogen activator (tPA) and mechanical thrombectomy (Powers et al, 2018). The limitations of tPA for acute ischemic stroke are a narrow time window of 4.5 h after stroke onset and potential risk of fatal intracranial hemorrhage (Fischer et al, 2017). The successful delivery of mechanical thrombectomy requires specialized stroke center and trained vascular surgeon, which are unavailable at most hospitals (Liebig et al, 2018). Ischemia stroke is known as the major cause of morbidity and mortality. The purpose of present study is to investigate the effects of BHD on angiogenesis in rats after cerebral ischemia/reperfusion (I/R) injury targeting Silent information regulator 1 (SIRT1) / Vascular endothelial growth factor (VEGF) pathway
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