دورية أكاديمية
A novel fluid resuscitation strategy modulates pulmonary transcription factor activation in a murine model of hemorrhagic shock
| العنوان: | A novel fluid resuscitation strategy modulates pulmonary transcription factor activation in a murine model of hemorrhagic shock |
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| المؤلفون: | Todd W. Costantini, Jessica Deree, J.O. Martins, James G. Putnam, Tercio de Campos, Raul Coimbra |
| المصدر: | Clinics, Vol 65, Iss 6, Pp 621-628 (2010) |
| بيانات النشر: | Elsevier España, 2010. |
| سنة النشر: | 2010 |
| المجموعة: | LCC:Medicine (General) |
| مصطلحات موضوعية: | Hypertonic saline, Pentoxifylline, NF-κB, CREB, CREB-binding protein, Medicine (General), R5-920 |
| الوصف: | 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-κB-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% HS + 25 mg/kg PTX). After four hours, lung samples were collected. NF-κB activation was assessed by measuring the levels of phosphorylated cytoplasmic inhibitor of kappa B (I-κB) and nuclear NF-κB p65 by western blot. NF-κB and CREB DNA-binding activity were measured by electrophoretic mobility shift assay (EMSA). Competition between NF-κB 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-κB phosphorylation, p65 phosphorylation, and NF-κB DNA binding compared with HSPTX. NF-κB-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-κB signaling and increased CREB-DNA binding activity. HSPTX may have therapeutic potential in the attenuation of ischemia-reperfusion injury observed after severe hemorrhagic shock. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1807-5932 1980-5322 |
| Relation: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322010000600010; https://doaj.org/toc/1807-5932; https://doaj.org/toc/1980-5322 |
| DOI: | 10.1590/S1807-59322010000600010 |
| URL الوصول: | https://doaj.org/article/88fb3f2e793b41e483a49b63f3c3116d |
| رقم الأكسشن: | edsdoj.88fb3f2e793b41e483a49b63f3c3116d |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 18075932 19805322 |
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| DOI: | 10.1590/S1807-59322010000600010 |