[Dexmedetomidine preconditioning protects against lung injury in hemorrhagic shock rats]

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.

Keywords: Choque hemorrágico; Dexmedetomidina; Dexmedetomidine; Hemorrhagic shock; Lesão pulmonar; Lung injury; Preconditioning; Pré‐condicionamento; Rat; Rato.

Figure 1

(A) SOD activity in the lung tissue. (B) MDA levels in the lung tissue. SOD, superoxide dismutase; MAD, malondialdehyde; Control, without hemorrhage; HS, hemorrhage shock; DEX1, 5 ug.kg⁻¹ dexmedetomidine; DEX2, 10 ug.kg⁻¹ dexmedetomidine. Values were presented as mean ± SEM, n = 8 for each group. *p < 0.05 vs. control group and #p < 0.05 vs. HS group.

Figure 2

(A) Representative picture of Bcl-2 and Bax. (B) The level of Bcl-2 and Bax. (C) Representative picture of caspase-3. (D) The level of caspase-3. Control, without hemorrhage; HS, hemorrhage shock; DEX1, 5 ug.kg⁻¹ dexmedetomidine; DEX2, 10 ug.kg⁻¹ dexmedetomidine. Values were presented as mean ± SEM, n = 8 for each group. *p < 0.05 vs. control group and #p < 0.05 vs. HS group.

Figure 3

(A) Protein in BAL. (B) WBC in BAL. BAL, bronchoalveolar lavage; Control, without hemorrhage; HS, hemorrhage shock; DEX1, 5 ug.kg⁻¹ dexmedetomidine; DEX2, 10 ug.kg⁻¹ dexmedetomidine. Values were presented as mean ± SEM, n = 8 for each group. *p < 0.05 vs. control group and #p < 0.05 vs. HS group.

Figure 4

(A) Representative TUNEL-sections of the lung tissue. (B) The cell apoptosis of the lung tissue. Control, without hemorrhage; HS, hemorrhage shock; DEX1, 5 ug.kg⁻¹ dexmedetomidine; DEX2, 10 ug.kg⁻¹ dexmedetomidine. Values were presented as mean ± SEM, n = 8 for each group. *p < 0.05 vs. HS group. Original magnification – 400×.

Figure 5

(A) Representative histological sections of the lung tissue. (B) The grade of the lung tissue. Control, without hemorrhage; HS, hemorrhage shock; DEX1, 5 ug.kg⁻¹ dexmedetomidine; DEX2: 1 ug.kg⁻¹ dexmedetomidine. Values were presented as mean ± SEM, n = 8 for each group. *p < 0.05 vs. HS group. Original magnification – 400×.