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Inflammation

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Tetramethylpyrazine Inhibits Platelet Adhesion and Inflammatory Response in Vascular Endothelial Cells by Inhibiting P38 MAPK and NF-κB Signaling Pathways

  • Han Zhang
  • Weiwei Tang
  • Shuang Wang
  • Junhua Zhang
  • Xiang FanEmail author
Original Article
  • 68 Downloads

Abstract

Damaged vascular endothelial cells after ischemic stroke release inflammatory cytokines and adhesion molecules, which could trigger platelet adhesion to vascular endothelial cells and platelet activation, and accelerate thrombus formation. Tetramethylpyrazine is the main bioactive component of Chuanxiong, which has demonstrated considerable protective effects in cerebrovascular diseases. However, the effect and mechanisms of tetramethylpyrazine on platelet adhesion to ischemia/reperfusion-injured endothelial cells have not been elucidated. In this study, we established an oxygen-glucose deprivation/reoxygenation (OGD/R)–induced brain microvascular endothelial cells (BMECs) injury model to investigate the protective effects of tetramethylpyrazine on platelet adhesion to endothelial cells and potential mechanisms. Experimental results showed that tetramethylpyrazine inhibited platelets adhesion to BMECs, alleviated expression of inflammatory cytokines and adhesion molecules on BMECs, and protected BMECs injured by OGD/R. Furthermore, tetramethylpyrazine could inhibit P38 MAPK and NF-κB activation in injured BMECs by OGD/R and inhibition of P38 MAPK with SB303580 and NF-κB with Bay-11-7082 attenuated the reduction of platelets adhesion to BMECs by tetramethylpyrazine. In conclusion, tetramethylpyrazine protected BMECs and inhibited platelets adhesion to BMECs after OGD/R injury, which was partially mediated by inhibiting P38 MAPK and NF-κB signaling pathways.

KEY WORDS

tetramethylpyrazine platelet adhesion inflammation NF-κB ischemia/reperfusion brain microvascular endothelial cells 

Abbreviations

Akt

serine/threonine kinase 1

Bax

BCL2-associated X

Bcl-2

B cell lymphoma-2

BMECs

brain microvascular endothelial cells

CCK-8

Cell Counting Kit-8

CXCR4

C-X-C motif chemokine receptor 4

CXCR7

C-X-C motif chemokine receptor 7

DMEM

Dulbecco’s Modified Eagle’s Medium

EBSS

Earle’s Balanced Salts

ERK

extracellular regulated MAP kinase

FBS

fetal bovine serum

GAPDH

glyceraldehyde-3-phosphate dehydrogenase

HIF-1α

hypoxia inducible factor 1 subunit alpha

HMGB1

high mobility group box 1

HO-1

heme oxygenase 1

ICAM-1

intercellular adhesion molecule-1

IL-1β

interleukin 1 beta

IL-6

interleukin 6

IL-8

interleukin 8

LDH

lactate dehydrogenase

LPS

lipopolysaccharide

MAPK

mitogen-activated protein kinase

MCP-1

macrophage cationic peptide 1

MLKL

mixed lineage kinase domain-like protein

NF-κB

nuclear factor-kappa B

Nrf2

nuclear factor, erythroid 2 like 2

OGD/R

oxygen-glucose deprivation/reoxygenation

PBS

phosphate-buffered saline

PGE1

prostaglandin E1

RIP1

receptor-interacting protein kinase 1

RIP3

receptor-interacting protein kinase 3

PIPES

piperazine-1,4-bis(2-ethanesulfonic acid)

SDF-1

stromal cell-derived factor 1

TLR4

toll-like receptor 4

TNF-α

tumor necrosis factor alpha

VCAM-1

vascular cell adhesion molecule 1

Notes

Author Contributions

HZ and XF contributed to the design of the study. HZ, WT, and SW were responsible for the data collection. HZ, WT, and XF analyzed the data. HZ and XF interpreted the data. XF drafted the manuscript. JZ revised the manuscript content. All the authors read and approved the final manuscript.

Funding information

This research was funded by National Natural Science Foundation of China (81622051) and Natural Science Foundation of Tianjin City (15JCYBJC54800).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Tianjin State Key Laboratory of Modern Chinese MedicineTianjin University of Traditional Chinese MedicineTianjinChina
  2. 2.Institute of Traditional Chinese MedicineTianjin University of Traditional Chinese MedicineTianjinChina

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