PMID- 25929655
OWN - NLM
STAT- MEDLINE
DCOM- 20151218
LR  - 20181113
IS  - 1471-2253 (Electronic)
IS  - 1471-2253 (Linking)
VI  - 15
DP  - 2015 May 1
TI  - The effect of dexmedetomidine on inflammatory response of septic rats.
PG  - 68
LID - 10.1186/s12871-015-0042-8 [doi]
LID - 68
AB  - 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 mug/kg (DEX5) 
      group, dexmedetomidine 10 mug/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-alpha (TNF-alpha) 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-alpha 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-kappaB 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-kappaB signaling pathway and are independent of 
      alpha2-adrenoceptor.
FAU - Zhang, Jianxing
AU  - Zhang J
AD  - Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080, 
      Guangzhou, Guangdong, China. jianxingzhang2014@163.com.
FAU - Wang, Zhipeng
AU  - Wang Z
AD  - Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080, 
      Guangzhou, Guangdong, China. zhipengwang2014@163.com.
FAU - Wang, Yan
AU  - Wang Y
AD  - Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080, 
      Guangzhou, Guangdong, China. yanwang_edu@163.com.
FAU - Zhou, Guobin
AU  - Zhou G
AD  - Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080, 
      Guangzhou, Guangdong, China. guobinzhou_edu@163.com.
FAU - Li, Hongying
AU  - Li H
AD  - Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080, 
      Guangzhou, Guangdong, China. hongyingli_edu@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150501
PL  - England
TA  - BMC Anesthesiol
JT  - BMC anesthesiology
JID - 100968535
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-6)
RN  - 0 (Myd88 protein, rat)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 2Y49VWD90Q (Yohimbine)
RN  - 67VB76HONO (Dexmedetomidine)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Bronchoalveolar Lavage Fluid/chemistry
MH  - Cytokines/antagonists & inhibitors
MH  - Dexmedetomidine/*pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Inflammation/drug therapy
MH  - Interleukin-6/antagonists & inhibitors
MH  - Ligation
MH  - MAP Kinase Signaling System/drug effects
MH  - Male
MH  - Myeloid Differentiation Factor 88/antagonists & inhibitors
MH  - NF-kappa B/antagonists & inhibitors
MH  - Random Allocation
MH  - Rats, Sprague-Dawley
MH  - Sepsis/*drug therapy
MH  - Toll-Like Receptor 4/antagonists & inhibitors
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors
MH  - Yohimbine/pharmacology
PMC - PMC4422264
EDAT- 2015/05/02 06:00
MHDA- 2015/12/19 06:00
PMCR- 2015/05/01
CRDT- 2015/05/02 06:00
PHST- 2014/10/09 00:00 [received]
PHST- 2015/04/20 00:00 [accepted]
PHST- 2015/05/02 06:00 [entrez]
PHST- 2015/05/02 06:00 [pubmed]
PHST- 2015/12/19 06:00 [medline]
PHST- 2015/05/01 00:00 [pmc-release]
AID - 10.1186/s12871-015-0042-8 [pii]
AID - 42 [pii]
AID - 10.1186/s12871-015-0042-8 [doi]
PST - epublish
SO  - BMC Anesthesiol. 2015 May 1;15:68. doi: 10.1186/s12871-015-0042-8.