Cargando…
Effects of Dl-3-n-butylphthalide on Cerebral Ischemia Infarction in Rat Model by Mass Spectrometry Imaging
Dl-3-n-butylphthalide (NBP) is a drug that is used in the treatment of ischaemic stroke. However, to the best of our knowledge, there are no systematic studies investigating the effects of dl-3-n-butylphtalide on the brain metabolism of small molecules. In this study, we first investigated the effec...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713418/ https://www.ncbi.nlm.nih.gov/pubmed/29165327 http://dx.doi.org/10.3390/ijms18112451 |
_version_ | 1783283421097754624 |
---|---|
author | Liu, Run-Zhe Fan, Chao-Xin Zhang, Zhi-Lin Zhao, Xin Sun, Yi Liu, Hui-Hui Nie, Zong-Xiu Pu, Xiao-Ping |
author_facet | Liu, Run-Zhe Fan, Chao-Xin Zhang, Zhi-Lin Zhao, Xin Sun, Yi Liu, Hui-Hui Nie, Zong-Xiu Pu, Xiao-Ping |
author_sort | Liu, Run-Zhe |
collection | PubMed |
description | Dl-3-n-butylphthalide (NBP) is a drug that is used in the treatment of ischaemic stroke. However, to the best of our knowledge, there are no systematic studies investigating the effects of dl-3-n-butylphtalide on the brain metabolism of small molecules. In this study, we first investigated the effects of dl-3-n-butylphthalide on the spatial distribution of small molecules in the brains of rats with permanent middle cerebral artery occlusion (pMCAO) using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI–TOF–MS) imaging. After pMCAO modelling or a sham operation, rats were given four mg/kg of dl-3-n-butylphthalide through the caudal vein or saline once a day for nine days. The degree of neurological deficit in rats was evaluated using the modified neurological severity score (mNSS). MALDI–TOF–MS imaging was used to observe the content and distribution of small molecules related to metabolism during focal cerebral ischaemia. Multiple reaction monitoring (MRM) mode with liquid chromatography tandem mass spectrometry (LC–MS/MS) was used to verify the results obtained from MALDI–TOF–MS imaging. These small molecules were found to be involved in glucose metabolism, ATP metabolism, the glutamate–glutamine cycle, malate aspartate shuttle, oxidative stress, and inorganic ion homeostasis. Of the 13 metabolites identified by MALDI–TOF–MS imaging, seven compounds, ATP, ADP, AMP, GMP, N-acetylaspartic acid, ascorbic acid and glutathione, were further validated by LC–MS/MS. Taken together, these results indicate that dl-3-n-butylphthalide significantly improved ATP metabolism, level of antioxidants, and sodium-potassium ion balance in a rat model of pMCAO. |
format | Online Article Text |
id | pubmed-5713418 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-57134182017-12-07 Effects of Dl-3-n-butylphthalide on Cerebral Ischemia Infarction in Rat Model by Mass Spectrometry Imaging Liu, Run-Zhe Fan, Chao-Xin Zhang, Zhi-Lin Zhao, Xin Sun, Yi Liu, Hui-Hui Nie, Zong-Xiu Pu, Xiao-Ping Int J Mol Sci Article Dl-3-n-butylphthalide (NBP) is a drug that is used in the treatment of ischaemic stroke. However, to the best of our knowledge, there are no systematic studies investigating the effects of dl-3-n-butylphtalide on the brain metabolism of small molecules. In this study, we first investigated the effects of dl-3-n-butylphthalide on the spatial distribution of small molecules in the brains of rats with permanent middle cerebral artery occlusion (pMCAO) using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI–TOF–MS) imaging. After pMCAO modelling or a sham operation, rats were given four mg/kg of dl-3-n-butylphthalide through the caudal vein or saline once a day for nine days. The degree of neurological deficit in rats was evaluated using the modified neurological severity score (mNSS). MALDI–TOF–MS imaging was used to observe the content and distribution of small molecules related to metabolism during focal cerebral ischaemia. Multiple reaction monitoring (MRM) mode with liquid chromatography tandem mass spectrometry (LC–MS/MS) was used to verify the results obtained from MALDI–TOF–MS imaging. These small molecules were found to be involved in glucose metabolism, ATP metabolism, the glutamate–glutamine cycle, malate aspartate shuttle, oxidative stress, and inorganic ion homeostasis. Of the 13 metabolites identified by MALDI–TOF–MS imaging, seven compounds, ATP, ADP, AMP, GMP, N-acetylaspartic acid, ascorbic acid and glutathione, were further validated by LC–MS/MS. Taken together, these results indicate that dl-3-n-butylphthalide significantly improved ATP metabolism, level of antioxidants, and sodium-potassium ion balance in a rat model of pMCAO. MDPI 2017-11-22 /pmc/articles/PMC5713418/ /pubmed/29165327 http://dx.doi.org/10.3390/ijms18112451 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Run-Zhe Fan, Chao-Xin Zhang, Zhi-Lin Zhao, Xin Sun, Yi Liu, Hui-Hui Nie, Zong-Xiu Pu, Xiao-Ping Effects of Dl-3-n-butylphthalide on Cerebral Ischemia Infarction in Rat Model by Mass Spectrometry Imaging |
title | Effects of Dl-3-n-butylphthalide on Cerebral Ischemia Infarction in Rat Model by Mass Spectrometry Imaging |
title_full | Effects of Dl-3-n-butylphthalide on Cerebral Ischemia Infarction in Rat Model by Mass Spectrometry Imaging |
title_fullStr | Effects of Dl-3-n-butylphthalide on Cerebral Ischemia Infarction in Rat Model by Mass Spectrometry Imaging |
title_full_unstemmed | Effects of Dl-3-n-butylphthalide on Cerebral Ischemia Infarction in Rat Model by Mass Spectrometry Imaging |
title_short | Effects of Dl-3-n-butylphthalide on Cerebral Ischemia Infarction in Rat Model by Mass Spectrometry Imaging |
title_sort | effects of dl-3-n-butylphthalide on cerebral ischemia infarction in rat model by mass spectrometry imaging |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713418/ https://www.ncbi.nlm.nih.gov/pubmed/29165327 http://dx.doi.org/10.3390/ijms18112451 |
work_keys_str_mv | AT liurunzhe effectsofdl3nbutylphthalideoncerebralischemiainfarctioninratmodelbymassspectrometryimaging AT fanchaoxin effectsofdl3nbutylphthalideoncerebralischemiainfarctioninratmodelbymassspectrometryimaging AT zhangzhilin effectsofdl3nbutylphthalideoncerebralischemiainfarctioninratmodelbymassspectrometryimaging AT zhaoxin effectsofdl3nbutylphthalideoncerebralischemiainfarctioninratmodelbymassspectrometryimaging AT sunyi effectsofdl3nbutylphthalideoncerebralischemiainfarctioninratmodelbymassspectrometryimaging AT liuhuihui effectsofdl3nbutylphthalideoncerebralischemiainfarctioninratmodelbymassspectrometryimaging AT niezongxiu effectsofdl3nbutylphthalideoncerebralischemiainfarctioninratmodelbymassspectrometryimaging AT puxiaoping effectsofdl3nbutylphthalideoncerebralischemiainfarctioninratmodelbymassspectrometryimaging |