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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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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).
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fig2: 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).

Mentions: The representative micrographs in Figure 2 represent eight samples in each group. Observed under light microscope by hematoxylin and eosin staining, rat lung tissue sections in sham group showed normal alveolar architecture (Figure 2(a)). Rats in CLP group exhibited marked lung histopathologic abnormalities, characterized by alveolar wall edema, congestion, leakage of microvessel, and inflammatory cells infiltration (Figure 2(b)). Small dose of dexmedetomidine failed to improve the histopathologic abnormalities. However, after treatment with medium and large doses of dexmedetomidine, lung tissues appeared relatively better, with a prominent decrease in inflammation response (Figures 2(d) and 2(e)) compared to CLP group. Findings of the pulmonary inflammation score paralleled the findings of the histopathological observation (Figure 3).


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)

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

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

fig2: 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).
Mentions: The representative micrographs in Figure 2 represent eight samples in each group. Observed under light microscope by hematoxylin and eosin staining, rat lung tissue sections in sham group showed normal alveolar architecture (Figure 2(a)). Rats in CLP group exhibited marked lung histopathologic abnormalities, characterized by alveolar wall edema, congestion, leakage of microvessel, and inflammatory cells infiltration (Figure 2(b)). Small dose of dexmedetomidine failed to improve the histopathologic abnormalities. However, after treatment with medium and large doses of dexmedetomidine, lung tissues appeared relatively better, with a prominent decrease in inflammation response (Figures 2(d) and 2(e)) compared to CLP group. Findings of the pulmonary inflammation score paralleled the findings of the histopathological observation (Figure 3).

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