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Rho-kinase inhibitor treatment prevents pulmonary inflammation and coagulation in lipopolysaccharide-induced lung injury.

Abstract：

INTRODUCTION:In the pathogenesis of sepsis-induced acute lung injury (ALI), the crosstalk between inflammation and coagulation plays a pivotal role. The aim of this study was to investigate the role of Rho kinase (ROCK) inhibitor in alleviating pulmonary inflammation and coagulation in lipopolysaccharide (LPS)-induced acute lung injury (ALI) models. METHODS:In the in vivo study, mice were randomized to four different groups: Control, Y-27632 (Y), LPS, and LPS+Y-27632 (LPS+Y). ALI was induced by intranasally administering LPS (10μg in 50μL PBS). Y-27632 (10mg/kg body weight,) was injected intraperitoneally at 18h and 1h before LPS challenge. Mice were euthanized at 3h or 8h post LPS challenge (N=8 per group). In the in vitro study, human pulmonary microvascular endothelial cells (HPMECs) were incubated with LPS alone (1μg/mL) or in combination with 10μM Y-27632 or 50μM BAY11-7082. Cells were pretreated with the inhibitors 30min before exposure to LPS. Three hours later, cells were isolated for subsequent analysis. RESULTS:The myeloperoxidase (MPO) activity and fibrinogen deposits in the lung tissue significantly decreased and the lung damage in ALI mouse was attenuated. Pretreatment with Y-27632 markedly reduced the LPS-induced expression of interleukins 1β and 6, and the activation of nuclear factor (NF)-κB. Furthermore, ROCK inhibitor treatment antagonized the expression of tissue factor (TF) and plasminogen activator inhibitor (PAI)-1 in lung tissue and HPMECs. CONCLUSIONS:ROCK inhibition protects against the endotoxin-induced pulmonary inflammation and coagulation via NF-kappaB pathway modulation.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Ding R,Zhao D,Li X,Liu B,Ma X

doi

10.1016/j.thromres.2016.12.020

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

59-64

eissn

0049-3848

issn

1879-2472

pii

S0049-3848(16)30675-2

journal_volume

150

pub_type

杂志文章

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