Dexmedetomidine Inhibits Inflammatory Reaction in Lung Tissues of Septic Rats by Suppressing TLR4/NF-κB Pathway

Chenghua Zhou,Yong Zhang,Ce Zhou,Yingchun Liu,Li Huang,He Huang,Fuzhao Lu,Yuqing Wu,Xin Li,Yangzi Zhu

doi:10.1155/2013/562154

Chenghua Zhou, Yong Zhang + Show 8 more

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https://doi.org/10.1155/2013/562154

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Abstract

Dexmedetomidine has been reported to reduce mortality in septic rats. This study was designed to investigate the effects of dexmedetomidine on inflammatory reaction in lung tissues of septic rats induced by CLP. After induction of sepsis, the rats were treated with normal saline or dexmedetomidine (5, 10, or 20 μg/kg). The survival rate of septic rats in 24 h was recorded. The inflammation of lung tissues was evaluated by HE stain. The concentrations of IL-6 and TNF-α in BALF and plasma were measured by ELISA. The expressions of TLR4 and MyD88 were measured by western blotting. The activation of NF-κB in rat lung tissues was assessed by western blotting and immunohistochemistry. It was found that the mortality rate and pulmonary inflammation were significantly increased in septic rats. IL-6 and TNF-α levels in BALF and plasma, NF-κB activity, and TLR4/MyD88 expression in rat lung tissues were markedly enhanced after CLP. Dexmedetomidine (10 and 20 μg/kg) significantly decreased mortality and pulmonary inflammation of septic rats, as well as suppressed CLP-induced elevation of TNF-α and IL-6 and inhibited TLR4/MyD88 expression and NF-κB activation. These results suggest that dexmedetomidine may decrease mortality and inhibit inflammatory reaction in lung tissues of septic rats by suppressing TLR4/MyD88/NF-κB pathway.

Highlights

Sepsis is a main problem in the intensive care unit (ICU) and carries a very high mortality rate
In order to clarify the mechanism through which dexmedetomidine inhibits pulmonary inflammation of septic rats induced by cecal ligation and puncture (CLP), we further investigated the expression of Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) in lung tissues
We investigated the effect of dexmedetomidine on mortality and inflammatory responses in lung tissues of septic rats induced by CLP

Summary

Introduction

Sepsis is a main problem in the intensive care unit (ICU) and carries a very high mortality rate. It involves a network of proinflammatory cytokines such as TNF-α and IL-6 which are overexpressed after various noxious insults, especially bacterial infections [1,2,3,4]. Dexmedetomidine’s analgesic effects are mediated in the dorsal horn of spinal cord, where it is thought to decrease the firing of ascending nociceptive neurons. These actions result in effective sedation and analgesia without respiratory depression and drug-dependency issues. The detailed mechanisms by which dexmedetomidine regulates inflammatory responses during endotoxemia have not been clearly revealed

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