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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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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.
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fig4: 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.

Mentions: As shown in Figure 4, the baseline values of IL-6 and TNF-α in the five groups were similar. However, both IL-6 and TNF-α levels in plasma and BALF of rats were markedly increased at 2, 4, and 6 hours after CLP operation compared to those in sham group. Medium and large doses of dexmedetomidine significantly inhibited the production of IL-6 and TNF-α in plasma and BALF induced by CLP. While small dose of dexmedetomidine did not obviously affect the levels of these proinflammatory cytokines in plasma and BALF of CLP rats.


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)

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

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

fig4: 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.
Mentions: As shown in Figure 4, the baseline values of IL-6 and TNF-α in the five groups were similar. However, both IL-6 and TNF-α levels in plasma and BALF of rats were markedly increased at 2, 4, and 6 hours after CLP operation compared to those in sham group. Medium and large doses of dexmedetomidine significantly inhibited the production of IL-6 and TNF-α in plasma and BALF induced by CLP. While small dose of dexmedetomidine did not obviously affect the levels of these proinflammatory cytokines in plasma and BALF of CLP rats.

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