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

Wu Y, Liu Y, Huang H, Zhu Y, Zhang Y, Lu F, Zhou C, Huang L, Li X, Zhou C - Mediators Inflamm. (2013)

Bottom Line: The expressions of TLR4 and MyD88 were measured by western blotting.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.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China.

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.

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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).
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fig7: 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).

Mentions: The nuclear positive staining represents the activated form of NF-kappa B. In CLP group, about 54% of alveolar epithelial cells expressed nuclear positive staining, as compared to about 18.5% in sham group (P < 0.01). The percentage of cells showing nuclear positive staining significantly decreased after treatment with dexmedetomidine at medium and high doses compared to CLP group (23.1 ± 5.8%, P < 0.01; 20.9 ± 5.3%, P < 0.01; versus 54.9 ± 12.8%, Figures 7 and 8).


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

Wu Y, Liu Y, Huang H, Zhu Y, Zhang Y, Lu F, Zhou C, Huang L, Li X, Zhou C - Mediators Inflamm. (2013)

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3649753&req=5

fig7: 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).
Mentions: The nuclear positive staining represents the activated form of NF-kappa B. In CLP group, about 54% of alveolar epithelial cells expressed nuclear positive staining, as compared to about 18.5% in sham group (P < 0.01). The percentage of cells showing nuclear positive staining significantly decreased after treatment with dexmedetomidine at medium and high doses compared to CLP group (23.1 ± 5.8%, P < 0.01; 20.9 ± 5.3%, P < 0.01; versus 54.9 ± 12.8%, Figures 7 and 8).

Bottom Line: The expressions of TLR4 and MyD88 were measured by western blotting.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.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221004, China.

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.

Show MeSH
Related in: MedlinePlus