Salvianolic Acid Alleviated Blood-Brain Barrier Permeability in Spontaneously Hypertensive Rats by Inhibiting Apoptosis in Pericytes via P53 and the Ras/Raf/MEK/ERK Pathway.
Alkenes
/ chemistry
Animals
Apoptosis
/ drug effects
Blood-Brain Barrier
/ drug effects
Cells, Cultured
Dose-Response Relationship, Drug
MAP Kinase Signaling System
/ drug effects
Molecular Structure
Pericytes
/ drug effects
Permeability
/ drug effects
Polyphenols
/ chemistry
Rats
Rats, Inbred SHR
Rats, Wistar
Structure-Activity Relationship
Tumor Suppressor Protein p53
/ metabolism
apoptosis
blood–brain barrier
hypertension
pericytes
salvianolic acid A
Journal
Drug design, development and therapy
ISSN: 1177-8881
Titre abrégé: Drug Des Devel Ther
Pays: New Zealand
ID NLM: 101475745
Informations de publication
Date de publication:
2020
2020
Historique:
received:
14
01
2020
accepted:
15
03
2020
entrez:
6
5
2020
pubmed:
6
5
2020
medline:
11
3
2021
Statut:
epublish
Résumé
To investigate the effect of salvianolic acid A (SA) on the permeability of blood-brain barrier (BBB) and brain microvascular pericyte apoptosis in spontaneously hypertensive rats (SHR). Evans Blue was used to determine the BBB permeability in control rats and SHR. Western blotting was used to evaluate the expression levels of relevant proteins in the pericytes isolated from the differentially treated animals. An in vitro model of hypertension was established by stimulating pericytes with angiopoietin-2 (Ang2). MTT assay was used to assess cell viability, and apoptosis and cell cycle distribution were analyzed by flow cytometry. SA attenuated BBB permeability in SHR in a dose-dependent manner. It downregulated pro-apoptotic proteins including p53, p21, Fas, FasL, cleaved-caspase 3/caspase 3 and Bax in the pericytes of SHR and upregulated CDK6, cyclin D1, CDK2, cyclin E and Bcl2. In addition, SA activated the Ras/Raf/MEK/ERK pathway in a dose-dependent manner by increasing the levels of Ras, Raf, p-MEK1, p-MEK2, p-ERK1 and p-ERK2. Finally, SA reduced Ang2-induced apoptosis of cerebral microvessels pericytes and decreased the proportion of cells in the G0/G1 phase of the cell cycle by inhibiting the p53 pathway and activating the Ras/Raf/MEK/ERK pathway. SA reduced BBB permeability in spontaneously hypertensive rats, possibly by inhibiting Ang2-induced apoptosis of pericytes by activating the Ras/Raf/MEK/ERK pathway.
Identifiants
pubmed: 32368011
doi: 10.2147/DDDT.S245959
pii: 245959
pmc: PMC7170553
doi:
Substances chimiques
Alkenes
0
Polyphenols
0
Tumor Suppressor Protein p53
0
salvianolic acid
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1523-1534Informations de copyright
© 2020 Wu et al.
Déclaration de conflit d'intérêts
The authors have no conflicts of interest to declare for this work.
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