A novel fluid resuscitation strategy modulates pulmonary transcription factor activation in a murine model of hemorrhagic shock
Clinics
;
65(6): 621-628, 2010. ilus
Article
in English
| LILACS
| ID: lil-553968
ABSTRACT
INTRODUCTION:
Combining the hemodynamic and immune benefits of hypertonic saline with the anti-inflammatory effects of the phosphodiesterase inhibitor pentoxifylline (HSPTX) as a hemorrhagic shock resuscitation strategy reduces lung injury when compared with the effects of Ringer's lactate (RL). We hypothesized that HSPTX exerts its anti-inflammatory effects by interfering with nuclear factor kappa B/cAMP response element-binding protein (NF-êB-CREB) competition for the coactivator CREB-binding protein (CBP) in lung tissue, thus affecting pro-inflammatory mediator production.METHODS:
Male Sprague-Dawley rats underwent 60 minutes of hemorrhagic shock to reach a mean arterial blood pressure of 35 mmHg followed by resuscitation with either RL or HSPTX (7.5 percent HS + 25 mg/kg PTX). After four hours, lung samples were collected. NF-êB activation was assessed by measuring the levels of phosphorylated cytoplasmic inhibitor of kappa B (I-êB) and nuclear NF-êB p65 by western blot. NF-êB and CREB DNA-binding activity were measured by electrophoretic mobility shift assay (EMSA). Competition between NF-êB and CREB for the coactivator CBP was determined by immunoprecipitation. Interleukin-8 (IL-8) levels in the lung were measured by ELISA.RESULTS:
RL resuscitation produced significantly higher levels of lung IL-8 levels, I-êB phosphorylation, p65 phosphorylation, and NF-êB DNA binding compared with HSPTX. NF-êB-CBP-binding activity was similar in both groups, whereas CREB-CBP-binding activity was significantly increased with HSPTX. CREB-DNA binding-activity increased to a greater level with HSPTX compared with RL.DISCUSSION:
HSPTX decreases lung inflammation following hemorrhagic shock compared with conventional resuscitation using RL through attenuation of NF-êB signaling and increased CREB-DNA binding activity. HSPTX may have therapeutic potential in the attenuation of ischemia-reperfusion...
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Index:
LILACS (Americas)
Main subject:
Phosphodiesterase Inhibitors
/
Shock, Hemorrhagic
/
Transcription Factors
/
Inflammation Mediators
/
Lung
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Clinics
Journal subject:
Medicine
Year:
2010
Type:
Article
Affiliation country:
United States
Institution/Affiliation country:
University of California San Diego School of Medicine/US
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