Abstract
Rationale: Houshiheisan (HSHS), a classic prescription in traditional Chinese medicine (TCM), has remarkable efficacy in the treatment of ischemic stroke.Objective: To investigate the pro-angiogenic effect and molecular mechanism of HSHS for stroke recovery.Methods and results: The rat permanent middle cerebral artery occlusion (pMCAO) model was constructed by suture method, HSHS (5.25 or 10.5 g/kg) and Ginaton (28 mg/kg) treatment was intragastrically administrated at 6 h after modeling which remained for 7 consecutive days. Pathological evaluation conducted by Hematoxylin–Eosin (HE) staining and the results showed that HSHS alleviated blood vessel edema, reduced the damage to blood vessels and neurons in the ischemic areas. Immunostaining, quantitative real-time fluorescence PCR results showed that HSHS up-regulated pro-angiogenic factors including platelet endothelial cell adhesion molecule-1 (cluster of differentiation 31 (CD31)), vascular endothelial growth factor (VEGF), vascular endothelial growth factor A (VEGFA), VEGF receptor 2 (VEGFR2), angiopoietin-1 (Ang-1), while down-regulated angiopoietin-2 (Ang-2), stromal cell derived factor-1 (SDF-1), and cxc chemokine receptor 4 (CXCR4) expression in infarct rat cortex, and similar results were obtained in subsequent Western blot experiment. Furthermore, CCK8 assay and transwell migration assay were performed to assess cell proliferation, migration, and tube formation. The medicated serum (MS) of HSHS appeared to have beneficial effects for immortalized human umbilical vein cells (Im-HUVECs) on proliferation and migration after persistence hypoxia. Western blot analysis revealed that the expression of hypoxia inducible factor-1α (HIF-1α), VEGFA, Ang-1, Ang-2, and CXCR4 were significantly up-regulated while Ang-2 was down-regulated by HSHS MS treatment compared with vehicle group in vitro.Conclusion: The present study suggests a novel application of HSHS as an effective angiogenic formula for stroke recovery.
Highlights
Ischemic cerebral stroke (ICS) is a worldwide disease characterized as high morbidity and mortality, which brings adverse outcomes such as the dysfunction in language, cognition, and motor [1]
HSHS alleviates the injury of neurons and blood vessels after cerebral ischemia in rats
Different degree of lesion appeared in the right cerebral cortex after permanent middle cerebral artery occlusion (pMCAO) modeling was observed by optical microscope (Figure 1A)
Summary
Ischemic cerebral stroke (ICS) is a worldwide disease characterized as high morbidity and mortality, which brings adverse outcomes such as the dysfunction in language, cognition, and motor [1]. Thrombolysis therapy brings great benefits to the patients with ICS, but it fails to effectively improve cerebral perfusion in those people [2]. Various sequelae such as hemiplegia, aphasia, and dysphagia still plague some patients which have received thrombolytic therapy [3]. Neuroprotectors perform pretty well in laboratory studies, they cannot replace thrombolytic therapy in current clinical applications. More effective treatments for ICS are still worth investigating
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