Dexmedetomidine preconditioning protects against lung injury in hemorrhagic shock rats / Pré-condicionamento com dexmedetomidina protege contra lesão pulmonar em ratos com choque hemorrágico

Abstract Background and objectives: Dexmedetomidine has demonstrated protective effects against lung injury in vitro. Here, we investigated whether dexmedetomidine preconditioning protected against lung injury in hemorrhagic shock rats. Methods: Male Sprague-Dawley rats were randomly divided into four groups (n = 8): control group, hemorrhagic shock group, 5 ug.kg-1 dexmedetomidine (DEX1) group, and 10 ug.kg-1 dexmedetomidine (DEX2) group. Saline or dexmedetomidine were administered over 20 min. 30 min after injection, hemorrhage was initiated in the hemorrhagic shock, DEX1 and DEX2 group. Four hours after resuscitation, protein and cellular content in bronchoalveolar lavage fluid, and the lung histopathology were measured. The malondialdehyde, superoxide dismutase, Bcl-2, Bax and caspase-3 were also tested in the lung tissue. Results: Compare with hemorrhagic shock group, 5 ug.kg-1 dexmedetomidine pretreatment reduced the apoptosis (2.25 ± 0.24 vs. 4.12 ± 0.42%, p < 0.05), histological score (1.06 ± 0.12 vs. 1.68 ± 0.15, p < 0.05) and protein (1.92 ± 0.38 vs. 3.95 ± 0.42 mg.mL-1, p < 0.05) and WBC (0.42 ± 0.11 vs. 0.92 ± 0.13 × 109/L, p < 0.05) in bronchoalveolar lavage fluid. Which is correlated with increased superoxide dismutase activity (8.35 ± 0.68 vs. 4.73 ± 0.44 U.mg-1 protein, p < 0.05) and decreased malondialdehyde (2.18 ± 0.19 vs. 3.28 ± 0.27 nmoL.mg-1 protein, p < 0.05). Dexmedetomidine preconditioning also increased the Bcl-2 level (0.55 ± 0.04 vs. 0.34 ± 0.05, p < 0.05) and decreased the level of Bax (0.46 ± 0.03 vs. 0.68 ± 0.04, p < 0.05), caspase-3 (0.49 ± 0.03 vs. 0.69 ± 0.04, p < 0.05). However, we did not observe any difference between the DEX1 and DEX2 groups for these (p > 0.05). Conclusion: Dexmedetomidine preconditioning has a protective effect against lung injury caused by hemorrhagic shock in rats. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation. But did not show a dose-dependent effect.

Resumo Justificativa e objetivos: Dexmedetomidina demonstrou efeitos protetores contra a lesão pulmonar in vitro. Neste estudo, investigamos se o pré-condicionamento com dexmedetomidina protege contra a lesão pulmonar em ratos com choque hemorrágico. Métodos: Ratos machos, Sprague-Dawley, foram aleatoriamente divididos em quatro grupos (n = 8): grupo controle, grupo com choque hemorrágico, grupo com 5 µg.kg-1 de dexmedetomidina (DEX1) e grupo com 10 µg.kg-1 de dexmedetomidina (DEX2). Solução salina ou dexmedetomidina foi administrada durante 20 minutos. Trinta minutos após a injeção, a hemorragia foi iniciada nos grupos choque hemorrágico, DEX1 e DEX2. Quatro horas após a ressuscitação, a proteína e o conteúdo celular no lavado broncoalveolar e a histopatologia pulmonar foram medidos. Malondialdeído, superóxido dismutase, Bcl-2, Bax e caspase-3 também foram testados no tecido pulmonar. Resultados: Na comparação com o grupo choque hemorrágico, o pré-tratamento com 5 ug.kg-1 de dexmedetomidina reduziu a apoptose (2,25 ± 0,24 vs. 4,12 ± 0,42%, p < 0,05), escore histológico (1,06 ± 0,12 vs. 1,68 ± 0,15, p < 0,05) e proteína (1,92 ± 0,38 vs. 3,95 ± 0,42 mg.mL-1, p < 0,05) e leucócitos (0,42 ± 0,11 vs. 0,92 ± 0,13 × 109/L, p < 0,05) no lavado broncoalveolar; o que está correlacionado com o aumento da atividade da superóxido dismutase (8,35 ± 0,68 vs. 4,73 ± 0,44 U.mg-1 de proteína, p < 0,05) e diminuição do malondialdeído (2,18 ± 0,19 vs. 3,28 ± 0,27 nmoL.mg-1 de proteína, p < 0,05). O pré-condicionamento com dexmedetomidina também aumentou o nível de Bcl-2 (0,55 ± 0,04 vs. 0,34 ± 0,05, p < 0,05) e diminuiu o nível de Bax (0,46 ± 0,03 vs. 0,68 ± 0,04, p < 0,05), caspase-3 (0,49 ± 0,03 vs. 0,69 ± 0,04, p < 0,05). No entanto, não houve diferença entre os grupos DEX1 e DEX2 para essas proteínas (p > 0,05). Conclusão: O pré-condicionamento com dexmedetomidina tem um efeito protetor contra a lesão pulmonar causada por choque hemorrágico em ratos. Os potenciais mecanismos envolvidos são a inibição da morte celular e a melhora da antioxidação. Porém, não mostrou um efeito dose-dependente.

[Dexmedetomidine preconditioning protects against lung injury in hemorrhagic shock rats]. / Pré­condicionamento com dexmedetomidina protege contra lesão pulmonar em ratos com choque hemorrágico.

BACKGROUND AND OBJECTIVES: Dexmedetomidine has demonstrated protective effects against lung injury in vitro. Here, we investigated whether dexmedetomidine preconditioning protected against lung injury in hemorrhagic shock rats. METHODS: Male Sprague-Dawley rats were randomly divided into four groups (n=8): control group, hemorrhagic shock group, 5ug.kg-1 dexmedetomidine (DEX1) group, and 10ug.kg-1 dexmedetomidine (DEX2) group. Saline or dexmedetomidine were administered over 20min. 30min after injection, hemorrhage was initiated in the hemorrhagic shock, DEX1 and DEX2 group. Four hours after resuscitation, protein and cellular content in bronchoalveolar lavage fluid, and the lung histopathology were measured. The malondialdehyde, superoxide dismutase, Bcl-2, Bax and caspase-3 were also tested in the lung tissue. RESULTS: Compare with hemorrhagic shock group, 5ug.kg-1 dexmedetomidine pretreatment reduced the apoptosis (2.25±0.24 vs. 4.12±0.42%, p<0.05), histological score (1.06±0.12 vs. 1.68±0.15, p<0.05) and protein (1.92±0.38 vs. 3.95±0.42mg.mL-1, p<0.05) and WBC (0.42±0.11 vs. 0.92±0.13×109/L, p<0.05) in bronchoalveolar lavage fluid. Which is correlated with increased superoxide dismutase activity (8.35±0.68 vs. 4.73±0.44U.mg-1 protein, p<0.05) and decreased malondialdehyde (2.18±0.19 vs. 3.28±0.27nmoL.mg-1 protein, p<0.05). Dexmedetomidine preconditioning also increased the Bcl-2 level (0.55±0.04 vs. 0.34±0.05, p<0.05) and decreased the level of Bax (0.46±0.03 vs. 0.68±0.04, p<0.05), caspase-3 (0.49±0.03 vs. 0.69±0.04, p<0.05). However, we did not observe any difference between the DEX1 and DEX2 groups for these (p>0.05). CONCLUSION: Dexmedetomidine preconditioning has a protective effect against lung injury caused by hemorrhagic shock in rats. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation. But did not show a dose-dependent effect.