Abstract
Purpose: To investigate the effect of dexmedetomidine in a rat model of acute lung injury (ALI), and the underlying mechanism.
 Methods: Acute lung injury (ALI) was induced in adult male Sprague Dawley rats (n = 27) using lipopolysaccharide (LPS). Three rat groups were used (9 rats/group): untreated control, LPS and treatment groups. Pathological lesions in rat pulmonary tissues were assessed and inflammatory scores determined. The levels TNF-α and IL-6 in BALF were determined using their respective enzyme-linked immunosorbent assay (ELISA) kits, while protein levels of p-IκB and NF-κB p65 were assessed by Western blotting.
 Results: Lung tissue damage was markedly mitigated in treatment mice, relative to LPS mice (p < 0.05). Inflammatory scores and population of neutrophils and macrophages increased significantly in LPS mice, relative to control, but decreased by dexmedetomidine exposure (p < 0.05). Similarly, TNF-α and IL-6 levels in pulmonary tissue homogenates of LPS rats were increased, relative to control rats, but were downregulated by dexmedetomidine exposure (p < 0.05). Moreover, dexmedetomidine downregulated the expressions of p-IκB and NF-κB p65 in pulmonary tissues (p < 0.05).
 Conclusion: Dexmedetomidine mitigates LPS-induced ALI in rats by blocking the activation of NF-κB and IκB, coupled with inhibition of the secretion of TNF-α and IL-6.
 Keywords: Acute lung injury, Dexmedetomidine, Inflammatory cytokines, NF-κB pathway, Sepsis
Highlights
Sepsis manifests when chemicals released into the systemic circulation to combat infection induce widespread inflammation in tissues
The present investigation was carried out to study the influence of dexmedetomidine on rat model of acute lung injury (ALI), and the mechanism involved
Alveolar wall thickness of rats in LPS group was significantly increased, and a large number of neutrophils and red blood cells (RBCs) exuded from the blood vessels, accompanied by edema fluid
Summary
Sepsis manifests when chemicals released into the systemic circulation to combat infection induce widespread inflammation in tissues This causes a sequence of lesions affecting multiple organs, leading to death in some cases. Sepsis occurs commonly in severe burns, multiple injuries and other diseases It leads to acute lung injury (ALI) and other complications, often characterized by aggregation of inflammatory cells and hydrops in the lungs, and pulmonary dysfunction. The present investigation was carried out to study the influence of dexmedetomidine on rat model of ALI, and the mechanism involved. With the exception of normal control group, the rats were injected intraperitoneally with LPS Rats in the treatment group received 40 g dexmedetomidine/kg bwt 15 min after LPS administration. Values of p < 0.05 were taken as indicative of significant differences
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