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 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 α2-adrenoceptor.
Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080, Guangzhou, Guangdong, China. jianxingzhang2014@163.com.
Jianxing
J
Zhang
Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080, Guangzhou, Guangdong, China. zhipengwang2014@163.com.
Zhipeng
Z
Wang
Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080, Guangzhou, Guangdong, China. yanwang_edu@163.com.
Yan
Y
Wang
Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080, Guangzhou, Guangdong, China. guobinzhou_edu@163.com.
Guobin
G
Zhou
Guangdong General Hospital, Guangdong Academy of Medical Sciences, 510080, Guangzhou, Guangdong, China. hongyingli_edu@163.com.
Hongying
H
Li
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000037:antagonists & inhibitors; D020927:Dexmedetomidine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000188:drug therapy; D008026:Ligation; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D015016:Yohimbine / Q000494:pharmacology; D000093242:Interleukin-6 Inhibitors
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D020927:Dexmedetomidine; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D015016:Yohimbine; D000093242:Interleukin-6 Inhibitors; C507781:Myd88 protein, rat