Cargando…

The effect of dexmedetomidine on inflammatory response of septic rats

BACKGROUND: Some studies have demonstrated dexmedetomidine has anti-inflammatory effect on septic rats. However, the mechanism of how dexmedetomidine exerts these effects is still remained unknown. This study was designed to investigate the mechanism of how dexmedetomidine inhibits the production of...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Jianxing, Wang, Zhipeng, Wang, Yan, Zhou, Guobin, Li, Hongying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422264/
https://www.ncbi.nlm.nih.gov/pubmed/25929655
http://dx.doi.org/10.1186/s12871-015-0042-8
_version_ 1782370027268210688
author Zhang, Jianxing
Wang, Zhipeng
Wang, Yan
Zhou, Guobin
Li, Hongying
author_facet Zhang, Jianxing
Wang, Zhipeng
Wang, Yan
Zhou, Guobin
Li, Hongying
author_sort Zhang, Jianxing
collection PubMed
description BACKGROUND: Some studies have demonstrated dexmedetomidine has anti-inflammatory effect on septic rats. However, the mechanism of how dexmedetomidine exerts these effects is still remained unknown. This study was designed to investigate the mechanism of how dexmedetomidine inhibits the production of inflammatory mediators in cecal ligation and puncturinduced septic rats. METHODS: 48 Sprague-Dawley rats were randomly divided into six groups: sham-operated (sham) group, cecal ligation and puncture (CLP) group, dexmedetomidine 5 μg/kg (DEX5) group, dexmedetomidine 10 μg/kg (DEX10) group,dexmedetomidine + yohimbine (DEX10 + Yoh) group and yohimibine group (Yoh). Blood, bronchoalveolarlavage fluid (BALF) and lung tissues in each group were collected at six hours after dexmedetomidine or yohimbine treatment,. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in BALF and plasma were measured by enzyme-linked immunosorbent assay (ELISA). Toll-like receptor-4(TLR4) and myeloid differerntiation factor(MyD88) expression were measuredby quantitative PCR, and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation were determined by western blott. RESULTS: Compared with CLP group, dexmedetomidine significantly decreased not only the production of TNF-α and IL-6 both in plasma and BALF, but also inhibited the expression of TLR4 and MyD88 in mRNA level and the activation of ERK1/2 and NF-κB in the lung tissues of CLP-induced septic rats. All these effects could not be reversed by yohimibine. CONCLUSIONS: Dexmedetomidine treatment can effectively reduce the generation of inflammatory mediators in the plasma and BALF of CLP-induced septic rats. These effects of dexmedetomidine rely on TLR4/MyD88/MAPK/ NF-κB signaling pathway and are independent of α(2)-adrenoceptor.
format Online
Article
Text
id pubmed-4422264
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-44222642015-05-07 The effect of dexmedetomidine on inflammatory response of septic rats Zhang, Jianxing Wang, Zhipeng Wang, Yan Zhou, Guobin Li, Hongying BMC Anesthesiol Research Article BACKGROUND: Some studies have demonstrated dexmedetomidine has anti-inflammatory effect on septic rats. However, the mechanism of how dexmedetomidine exerts these effects is still remained unknown. This study was designed to investigate the mechanism of how dexmedetomidine inhibits the production of inflammatory mediators in cecal ligation and puncturinduced septic rats. METHODS: 48 Sprague-Dawley rats were randomly divided into six groups: sham-operated (sham) group, cecal ligation and puncture (CLP) group, dexmedetomidine 5 μg/kg (DEX5) group, dexmedetomidine 10 μg/kg (DEX10) group,dexmedetomidine + yohimbine (DEX10 + Yoh) group and yohimibine group (Yoh). Blood, bronchoalveolarlavage fluid (BALF) and lung tissues in each group were collected at six hours after dexmedetomidine or yohimbine treatment,. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in BALF and plasma were measured by enzyme-linked immunosorbent assay (ELISA). Toll-like receptor-4(TLR4) and myeloid differerntiation factor(MyD88) expression were measuredby quantitative PCR, and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation were determined by western blott. RESULTS: Compared with CLP group, dexmedetomidine significantly decreased not only the production of TNF-α and IL-6 both in plasma and BALF, but also inhibited the expression of TLR4 and MyD88 in mRNA level and the activation of ERK1/2 and NF-κB in the lung tissues of CLP-induced septic rats. All these effects could not be reversed by yohimibine. CONCLUSIONS: Dexmedetomidine treatment can effectively reduce the generation of inflammatory mediators in the plasma and BALF of CLP-induced septic rats. These effects of dexmedetomidine rely on TLR4/MyD88/MAPK/ NF-κB signaling pathway and are independent of α(2)-adrenoceptor. BioMed Central 2015-05-01 /pmc/articles/PMC4422264/ /pubmed/25929655 http://dx.doi.org/10.1186/s12871-015-0042-8 Text en © Zhang et al.; licensee BioMed Central. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhang, Jianxing
Wang, Zhipeng
Wang, Yan
Zhou, Guobin
Li, Hongying
The effect of dexmedetomidine on inflammatory response of septic rats
title The effect of dexmedetomidine on inflammatory response of septic rats
title_full The effect of dexmedetomidine on inflammatory response of septic rats
title_fullStr The effect of dexmedetomidine on inflammatory response of septic rats
title_full_unstemmed The effect of dexmedetomidine on inflammatory response of septic rats
title_short The effect of dexmedetomidine on inflammatory response of septic rats
title_sort effect of dexmedetomidine on inflammatory response of septic rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422264/
https://www.ncbi.nlm.nih.gov/pubmed/25929655
http://dx.doi.org/10.1186/s12871-015-0042-8
work_keys_str_mv AT zhangjianxing theeffectofdexmedetomidineoninflammatoryresponseofsepticrats
AT wangzhipeng theeffectofdexmedetomidineoninflammatoryresponseofsepticrats
AT wangyan theeffectofdexmedetomidineoninflammatoryresponseofsepticrats
AT zhouguobin theeffectofdexmedetomidineoninflammatoryresponseofsepticrats
AT lihongying theeffectofdexmedetomidineoninflammatoryresponseofsepticrats
AT zhangjianxing effectofdexmedetomidineoninflammatoryresponseofsepticrats
AT wangzhipeng effectofdexmedetomidineoninflammatoryresponseofsepticrats
AT wangyan effectofdexmedetomidineoninflammatoryresponseofsepticrats
AT zhouguobin effectofdexmedetomidineoninflammatoryresponseofsepticrats
AT lihongying effectofdexmedetomidineoninflammatoryresponseofsepticrats