Beneficial effect of magnesium lithospermate B on cerebral ischemia-reperfusion injury in rats involves the regulation of miR-107/glutamate transporter 1 pathway.
Eur J Pharmacol
; 766: 91-8, 2015 Nov 05.
Article
in En
| MEDLINE
| ID: mdl-26420356
ABSTRACT
Recent studies uncovered that glutamate accumulation following cerebral ischemia-reperfusion (I/R) was related to the dysfunction of miR-107/glutamate transporter-1(GLT-1) pathway and magnesium lithospermate B (MLB) possesses the pharmacological activity of anti-excitotoxicity. This study aims to explore whether MLB is able to protect rat brain from excitatory neurotoxicity during I/R by modulating miR-107/GLT-1 pathway. Rats were subjected to 2h of cerebral ischemia following by 24h of reperfusion to establish an I/R injury model, which showed an increase in neurological deficit score, infarct volume and cellular apoptosis concomitant with glutamate accumulation, miR-107 elevation and GLT-1 down-regulation. Administration of MLB reduced I/R-induced cerebral injury accompanied by a reverse in glutamate accumulation, miR-107 and GLT-1 expression. Next, we examined the association of MLB with miR-107/GLT-1 pathway in a nerve cell hypoxia/reoxygenation (H/R) injury model. H/R treatment increased the nerve cells apoptosis concomitant with glutamate accumulation and miR-107 elevation, and suppressed GLT-1 expression, mimicking our in vivo findings. All these effects were reversed in the presence of MLB, confirming a strong correlation between MLB and miR-107/GLT-1 pathway. Based on these observations, we conclude that MLB is able to protect the rat brain from excitatory neurotoxicity during I/R through the regulation of miR-107/GLT-1 pathway.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drugs, Chinese Herbal
/
Reperfusion Injury
/
Neuroprotective Agents
/
Infarction, Middle Cerebral Artery
/
Excitatory Amino Acid Transporter 2
/
MicroRNAs
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Eur J Pharmacol
Year:
2015
Document type:
Article
Affiliation country:
China