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Sodium tanshinone IIA sulfonate ameliorates cerebral ischemic injury through regulation of angiogenesis
Vascular remodeling and neuroprotection are two major adaptable methods for treating ischemic stroke. Edaravone is a protective agent for the treatment of stroke and was used as a positive control in the present study. Sodium tanshinone IIA sulfonate (STS) has demonstrated therapeutic clinical effec...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383733/ https://www.ncbi.nlm.nih.gov/pubmed/34504576 http://dx.doi.org/10.3892/etm.2021.10556 |
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author | Xu, Jiazhen Zhang, Pei Chen, Yao Xu, Yulan Luan, Pengwei Zhu, Yuying Zhang, Jiange |
author_facet | Xu, Jiazhen Zhang, Pei Chen, Yao Xu, Yulan Luan, Pengwei Zhu, Yuying Zhang, Jiange |
author_sort | Xu, Jiazhen |
collection | PubMed |
description | Vascular remodeling and neuroprotection are two major adaptable methods for treating ischemic stroke. Edaravone is a protective agent for the treatment of stroke and was used as a positive control in the present study. Sodium tanshinone IIA sulfonate (STS) has demonstrated therapeutic clinical effects in cerebral infarction in China, while its mechanisms of action in ischemic stroke have remained elusive. The angiogenesis and neuroprotective effects of STS were evaluated in a rat model induced by middle cerebral artery occlusion and 3 days of reperfusion. When used at the same dose, the magnitude of the therapeutic effect of STS was similar to that of edaravone in terms of decreased blood-brain barrier damage as indicated by reduced Evans blue leakage, improved neurological deficits, alleviated cerebral edema and inhibition of histopathological changes caused by ischemia/reperfusion. The TUNEL assay demonstrated that the ability of STS to inhibit neuronal apoptosis was equivalent to that of edaravone. Immunofluorescence detection of CD31 and α-smooth muscle actin indicated that the vascular density was significantly reduced in the vehicle group compared with that in the sham operation group, STS increased the microvessel density in the ischemic area. Furthermore, in the vehicle group the protein expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR) as determined by fluorescence microscopy and immunohistochemistry was significantly reduced compared with that in the sham group. However, STS promoted their expression compared to the vehicle group respectively, and increaed the mRNA expression of VEGF, VEGFR, CD31 and angiopoietin-1 as determined by reverse transcription-quantitative PCR, but these changes were not significant or not present for edaravone apart from Ang-1. In conclusion, STS protected against ischemic brain injury by promoting angiogenesis in ischemic areas and inhibiting neuronal apoptosis. These results provide a potential treatment for stroke recovery. |
format | Online Article Text |
id | pubmed-8383733 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-83837332021-09-08 Sodium tanshinone IIA sulfonate ameliorates cerebral ischemic injury through regulation of angiogenesis Xu, Jiazhen Zhang, Pei Chen, Yao Xu, Yulan Luan, Pengwei Zhu, Yuying Zhang, Jiange Exp Ther Med Articles Vascular remodeling and neuroprotection are two major adaptable methods for treating ischemic stroke. Edaravone is a protective agent for the treatment of stroke and was used as a positive control in the present study. Sodium tanshinone IIA sulfonate (STS) has demonstrated therapeutic clinical effects in cerebral infarction in China, while its mechanisms of action in ischemic stroke have remained elusive. The angiogenesis and neuroprotective effects of STS were evaluated in a rat model induced by middle cerebral artery occlusion and 3 days of reperfusion. When used at the same dose, the magnitude of the therapeutic effect of STS was similar to that of edaravone in terms of decreased blood-brain barrier damage as indicated by reduced Evans blue leakage, improved neurological deficits, alleviated cerebral edema and inhibition of histopathological changes caused by ischemia/reperfusion. The TUNEL assay demonstrated that the ability of STS to inhibit neuronal apoptosis was equivalent to that of edaravone. Immunofluorescence detection of CD31 and α-smooth muscle actin indicated that the vascular density was significantly reduced in the vehicle group compared with that in the sham operation group, STS increased the microvessel density in the ischemic area. Furthermore, in the vehicle group the protein expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR) as determined by fluorescence microscopy and immunohistochemistry was significantly reduced compared with that in the sham group. However, STS promoted their expression compared to the vehicle group respectively, and increaed the mRNA expression of VEGF, VEGFR, CD31 and angiopoietin-1 as determined by reverse transcription-quantitative PCR, but these changes were not significant or not present for edaravone apart from Ang-1. In conclusion, STS protected against ischemic brain injury by promoting angiogenesis in ischemic areas and inhibiting neuronal apoptosis. These results provide a potential treatment for stroke recovery. D.A. Spandidos 2021-10 2021-08-04 /pmc/articles/PMC8383733/ /pubmed/34504576 http://dx.doi.org/10.3892/etm.2021.10556 Text en Copyright: © Xu et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Xu, Jiazhen Zhang, Pei Chen, Yao Xu, Yulan Luan, Pengwei Zhu, Yuying Zhang, Jiange Sodium tanshinone IIA sulfonate ameliorates cerebral ischemic injury through regulation of angiogenesis |
title | Sodium tanshinone IIA sulfonate ameliorates cerebral ischemic injury through regulation of angiogenesis |
title_full | Sodium tanshinone IIA sulfonate ameliorates cerebral ischemic injury through regulation of angiogenesis |
title_fullStr | Sodium tanshinone IIA sulfonate ameliorates cerebral ischemic injury through regulation of angiogenesis |
title_full_unstemmed | Sodium tanshinone IIA sulfonate ameliorates cerebral ischemic injury through regulation of angiogenesis |
title_short | Sodium tanshinone IIA sulfonate ameliorates cerebral ischemic injury through regulation of angiogenesis |
title_sort | sodium tanshinone iia sulfonate ameliorates cerebral ischemic injury through regulation of angiogenesis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383733/ https://www.ncbi.nlm.nih.gov/pubmed/34504576 http://dx.doi.org/10.3892/etm.2021.10556 |
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