Dexmedetomidine Protects Against Traumatic Brain Injury-Induced Acute Lung Injury in Mice

Abstract

BACKGROUND Traumatic brain injury (TBI) leads to acute lung injury (ALI), in which the inflammatory response plays an important role in its pathophysiology. Recent studies suggest that dexmedetomidine (Dex) plays a protective role in acute inflammatory diseases. However, whether Dex has a protective effect on TBI-induced ALI is not clear. The aim of this study was to investigate the effect of Dex on TBI-induced ALI in mice. MATERIAL AND METHODS Mice were randomly divided into 5 groups: 1) sham group; 2) TBI group; 3) TBI+Dex group; 4) TBI+atipamezole (Atip) group; and 5) TBI+Dex+Atip group. Dex (50 μg/kg) was intraperitoneal injected immediately after TBI. The α2 adrenergic antagonist Atip (250 μg/kg) was intraperitoneal injected 15 minutes prior to Dex treatment. Then 24 hours later, the protein concentration in the bronchoalveolar lavage fluid (BALF), lung wet to dry weight ratio, hematoxylin and eosin (H&E) staining of lungs, the level of high-mobility group box protein 1(HMGB1) in serum, and the receptor for advanced glycation end products (RAGE) expression in lung were detected. RESULTS Dex ameliorated the score of lung histological examination, as well as the severity of pulmonary edema and permeability. Moreover, Dex was observed to significantly suppress the expression of HMGBI and RAGE. However, the protective effects of Dex were partially reversed by the administration of Atip. CONCLUSIONS Dex may protect against TBI-induced ALI via the HMGB1-RAGE signal pathway, and this protective effect is partly dependent on its α2 adrenoceptor agonist action.

Figure 1

Dexmedetomidine (Dex) ameliorated TBI-induced ALI in mice. After 24 hours of TBI, lung tissue and the BALF in each group were collected. (A) The example of micrographic images (200×) from the sham group, the TBI group, the TBI+Dex group, the TBI+Atip group, and the TBI+Dex+Atip group. (B) Histopathological lung injury scores in each group. (C) Total protein concentration in the BALF of mice in each group. (D) The lung wet-to-dry ratio. The values are presented as the means ±SEM. * P<0.05, ** P<0.01 versus the sham group, ^# P<0.05, ^## P<0.01 versus the TBI group, ^@ P<0.05, ^@@ P<0.01 versus the TBI+Dex group.

Figure 2

Dexmedetomidine (Dex) negatively regulated HMGB1-RAGE pathway. At 24 hours of TBI, lung tissues and blood in each group were collected. (A) HMGB1 level in serum of mice in each group. (B) The mRNA expression of RAGE in lung tissues. (C) Western blot analysis for RAGE in lung tissues. (D) Density quantification of RAGE. The values are presented as the means ±SEM. ** P<0.01 versus the sham group, ^## P<0.01 versus the TBI group, ^@@ P<0.01 versus the TBI+Dex group.