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Int. J. Mol. Sci. 2017, 18(11), 2451; doi:10.3390/ijms18112451

Effects of Dl-3-n-butylphthalide on Cerebral Ischemia Infarction in Rat Model by Mass Spectrometry Imaging

1
National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China
2
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
3
Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, China
*
Author to whom correspondence should be addressed.
Received: 18 September 2017 / Revised: 9 November 2017 / Accepted: 14 November 2017 / Published: 22 November 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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. View Full-Text
Keywords: dl-3-n-butylphthalide; permanent middle cerebral artery occlusion (pMCAO); matrix-assisted laser desorption time of flight ionization mass spectrometry imaging (MALDI–TOF–MS imaging); metabolites dl-3-n-butylphthalide; permanent middle cerebral artery occlusion (pMCAO); matrix-assisted laser desorption time of flight ionization mass spectrometry imaging (MALDI–TOF–MS imaging); metabolites
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Liu, R.-Z.; Fan, C.-X.; Zhang, Z.-L.; Zhao, X.; Sun, Y.; Liu, H.-H.; Nie, Z.-X.; Pu, X.-P. Effects of Dl-3-n-butylphthalide on Cerebral Ischemia Infarction in Rat Model by Mass Spectrometry Imaging. Int. J. Mol. Sci. 2017, 18, 2451.

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