Volume 29, Issue 4, 2020
DOI: 10.24205/03276716.2020.837
Dexmedetomidine Mitigates LPS-Induced Acute Lung Injury in Rats Through HMGB1-Mediated Anti-Inflammatory and Antioxidant Mechanisms
Abstract
Purpose: To investigate the effect of dexmedetomidine on lipopolysaccharide (LPS)-induced acute lung injury in rats, and the underlying mechanism.
Methods: Healthy male SD rats (n=54) were randomly divided into three groups: normal, model and dexmedetomidine groups, with 18 rats in each group. Rats in the model and dexmedetomidine groups were given LPS at a dose of 8 mg/kg, to establish a model of acute lung injury. Rats in the dexmedetomidine group were injected intraperitoneallywith dexmedetomidine at a dose of 50 μg/kg prior to establishment of the model, while rats in the normal group received intraperitoneal injection of normal saline in place of dexmedetomidine. Hematoxylin and eosin (H&E) staining was used to observe changes in lung tissue in each group.Changes in wet/dry weight ratio of lung tissue were compared among the groups. Enzyme-linked immunosorbent assay was used to determine the expressions of inflammation indices i.e. interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (L-1β)] in lung tissue. Levels of MDA were measured with thiobarbituric acid method. Superoxide dismutase (SOD) activity was assayed through enzyme rate method, while nitric oxide was measured using nitrate reductase assay.The expression levels of high mobility group protein B1 (HMGB1), p-PI3K, p-Akt, p-IκB, p-NF-κB, and Toll-like receptor 4 (TLR4) in lung tissue were determined with Western blotting.
Results:In the normal group, lung tissue structure was intact, with clear alveolar cavity, non-edematous alveolar space, and absence of inflammatory infiltration.In the model group,lung tissue was disordered, with thinner alveolar cavity, widenedand thicker alveolar space, and inflammatory cell infiltration. Lung tissue of the dexmedetomidine group was significantly improved, relative to the model group.Compared with the normal group, lung wet/dry ratio, and levels of inflammatory indices (MDA, NO and HMGB1, p-PI3K, p-Akt, p-IκB, p-NF-κB, and TLR4 were significantly increased in the model group, while the SOD level was significantly reduced (p<0.05). However, compared with the model group, wet/dry ratio of lung, MDA, NO and HMGB1, p-PI3K, p-Akt, p-IκB, p-NF-κB, and TLR4 levels were significantly decreased, while SOD levels increased significantly (p<0.05).
Conclusion: Dexmedetomidine mitigates LPS-induced acute lung injury in rats through HMGB1-mediated anti-inflammatory antioxidant effect, which may be closely related to the TLR4/NF-κB and PI3K/Akt pathways.
Keywords
Dexmedetomidine, HMGB1, anti-inflammatory, antioxidant effects, LPS, acute lung injury