Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013:2013:562154.
doi: 10.1155/2013/562154. Epub 2013 Apr 8.

Dexmedetomidine inhibits inflammatory reaction in lung tissues of septic rats by suppressing TLR4/NF-κB pathway

Yuqing Wu  1 , Yingchun Liu, He Huang, Yangzi Zhu, Yong Zhang, Fuzhao Lu, Ce Zhou, Li Huang, Xin Li, Chenghua Zhou
Affiliations

Dexmedetomidine inhibits inflammatory reaction in lung tissues of septic rats by suppressing TLR4/NF-κB pathway

Yuqing Wu et al. Mediators Inflamm. 2013.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Effect of dexmedetomidine on survival curves of septic rats induced by CLP. Sham: sham operation group; CLP: cecal ligation and puncture operation group; Small: 5 μg/kg dexmedetomidine treatment group; Medium: 10 μg/kg dexmedetomidine treatment group; Large: 20 μg/kg dexmedetomidine treatment group. n = 8. The survival rate at 24 h after operation was analyzed. *P < 0.01, versus sham group; # P < 0.01, versus CLP group.
Figure 2
Figure 2
Microscopic findings of the lung tissues stained with hematoxylin and eosin. (a) Sham operation group. The lung tissues showed normal to minimal pulmonary inflammation. (b) CLP group. The lung tissues showed severe pulmonary inflammation. (c) Small dose (5 μg/kg) group. The lung tissues showed severe pulmonary inflammation. (d) Medium dose (10 μg/kg) group. The lung tissues showed moderate pulmonary inflammation. (e) Large dose (20 μg/kg) group. The lung tissues showed mild pulmonary inflammation. (magnification 200x).
Figure 3
Figure 3
Pulmonary inflammation scores of rats from different groups. Sham: sham operation group; CLP: cecal ligation and puncture operation group; Small: 5 μg/kg dexmedetomidine treatment group; Medium: 10 μg/kg dexmedetomidine treatment group; Large: 20 μg/kg dexmedetomidine treatment group. Data are expressed as mean ± SD, n = 8. *P < 0.01, versus sham group; # P < 0.01, versus CLP group.
Figure 4
Figure 4
Levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in plasma (n = 6) and bronchoalveolar lavage fluid (BALF) (n = 8). (a) IL-6 in plasma. (b) TNF-α in plasma. (c) IL-6 in BALF. (d) TNF-α in BALF. Data are expressed as mean ± SD. *P < 0.01, versus sham group; # P < 0.01, versus CLP group.
Figure 5
Figure 5
Effect of dexmedetomidine on TLR4 and MyD88 expression in lung tissues of septic rats by western blotting. Sham: sham operation group; CLP: cecal ligation and puncture operation group; Small: 5 μg/kg dexmedetomidine treatment group; Medium: 10 μg/kg dexmedetomidine treatment group; Large: 20 μg/kg dexmedetomidine treatment group. GAPDH: glyceraldehyde phosphate dehydrogenase. Data are expressed as mean ± SD, n = 8. *P < 0.01, versus sham group; # P < 0.01, versus CLP group.
Figure 6
Figure 6
Effect of dexmedetomidine on NF-κB p-65 activity in lung nuclear extracts of septic rats by western blotting. Sham: sham operation group; CLP: cecal ligation and puncture operation group; Small: 5 μg/kg dexmedetomidine treatment group; Medium: 10 μg/kg dexmedetomidine treatment group; Large: 20 μg/kg dexmedetomidine treatment group. GAPDH: glyceraldehyde phosphate dehydrogenase. Data are expressed as mean ± SD, n = 8. *P < 0.01, versus sham group; # P < 0.01, versus CLP group.
Figure 7
Figure 7
Effect of dexmedetomidine on NF-κB p-65 activation in lung tissues of septic rats by immunohistochemistry staining. (a) Sham operation group; (b) cecal ligation and puncture operation group; (c) 5 μg/kg dexmedetomidine treatment group; (d) 10 μg/kg dexmedetomidine treatment group; (e) 20 μg/kg dexmedetomidine treatment group (magnification 400x).
Figure 8
Figure 8
Effect of dexmedetomidine on NF-κB p-65 activation in lung tissues of septic rats by immunohistochemistry staining. Sham: sham operation group; CLP: cecal ligation and puncture operation group; Small: 5 μg/kg dexmedetomidine treatment group; Medium: 10 μg/kg dexmedetomidine treatment group; Large: 20 μg/kg dexmedetomidine treatment group. The degree of NF-κB activation was indicated as percentage of nuclear NF-κB p-65 positive cells to total alveolar epithelial cells. Data are expressed as mean ± SD, n = 8. *P < 0.01, versus sham group; # P < 0.01, versus CLP group.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Wakabayashi G, Gelfand JA, Jung WK, Connolly RJ, Burke JF, Dinarello CA. Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock-like state and tissue injury in rabbits without endotoxemia: comparison to Escherichia coli. The Journal of Clinical Investigation. 1991;87(6):1925–1935. - PMC - PubMed
    1. Casey LC, Balk RA, Bone RC. Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Annals of Internal Medicine. 1993;119(8):771–778. - PubMed
    1. Marty C, Misset B, Tamion F, Fitting C, Carlet J, Cavaillon JM. Circulating interleukin-8 concentrations in patients with multiple organ failure of septic and nonseptic origin. Critical Care Medicine. 1994;22(4):673–679. - PubMed
    1. Damas P, Reuter A, Gysen P, Demonty J, Lamy M, Franchimont P. Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans. Critical Care Medicine. 1989;17(10):975–978. - PubMed
    1. Delong P, Murray JA, Cook CK. Mechanical ventilation in the management of acute respiratory distress syndrome. Seminars in Dialysis. 2006;19(6):517–524. - PubMed

Publication types