Abstract:
Objective To investigate the protective effects of sodium valproate on lung function in rats with 50% total body surface area(TBSA) Ⅲ degree scalded injury.
Methods Forty male SD rats were randomly divided into 2 groups: simple scald + saline group and sodium valproate group, with 20 rats in each group. After anesthesia with 50 mg/kg sodium pentobarbital and skin preparation, the rats in the 2 groups were soaked in water bath at 96 ℃ for 15 s on the back, 15 s on the lower extremities and 8 s on the abdomen to make 50%TBSA Ⅲ degree scald model. Immediately after scald, sodium valproate group was given sodium valproate treatment (300 mg/kg, intraperitoneal injection), and simple scald + saline group was given 0.9% sodium chloride solution control treatment (300 mg/kg, intraperitoneal injection). At 6 and 24 h after scald, the rats in the 2 groups were killed by abdominal aorta blood collection method, and about 1 g of lung tissue was obtained by midline thoracotomy for standby. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL-6) and IL-8 in lung tissue of rats in the 2 groups were detected by enzyma-linked immunosorbent assay (ELISA) at 6 and 24 h after scald, respectively. Evans blue method was used to detect pulmonary microvascular permeability; dry/wet weight method was used to detect the moisture content of lung tissue; the fixed embedding of lung tissue was followed by hematoxylin-eosin (HE) staining, and the lung histopathological changes of the 2 groups were observed under optical microscope; Ahshcroft fibrosis score was used to score the degree of pulmonary fibrosis in the lung tissue sections after HE staining; lung injury score was performed by double-blind method. Data were compared by t test.
Results At 6 h after scald, the levels of TNF-α, IL-6 and IL-8 in sodium valproate group were (2 412.3±105.1), (1 724.2±168.4) and (1 343.3±103.2) pg/mL, respectively, which were significantly lower than those in simple scald + saline group [(2 861.1±121.3), (2 392.1±184.2), (1 691.5±121.4) pg/mL], and there were statistically significant differences between the 2 groups (t=2.154, 2.612, 2.741; P< 0.05); at 24 h after scald, the levels of TNF-α, IL-6 and IL-8 in sodium valproate group were (1 823.7±97.3), (927.2±106.1) and (862.3±80.5) pg/mL, respectively, which were significantly lower than those in simple scald + saline group [(2 437.5±109.7), (1 721.6±86.5), (1 341.1±97.4) pg/mL], and the differences between the 2 groups were statistically significant (t=2.231, 2.529, 2.394; P<0.05). At 6 h after scald, the content of Evans blue and the moisture content of lung tissue in sodium valproate group were (59.22±1.24) μg/g and (78.37±1.32)%, respectively, which were significantly lower than those in simple scald + saline group [(71.21±1.28) μg/g, (83.13±1.43)%], the differences between the 2 groups were statistically significant (t= 2.219, 2.463; P<0.05); at 24 h after scald, the content of Evans blue and moisture content of lung tissue in sodium valproate group were (71.21±1.28) μg/g and (83.13±1.43)%, respectively, which were significantly lower than those in simple scald + saline group [(78.34±1.31) μg/g, (85.31±1.35) %], the differences between the 2 groups were statistically significant (t=2.851, 2.785; P<0.05). Observation under optical microscope showed that, at 6 h after scald, there was alveolar space in the lung tissue of rats in the simple scald+ saline group, but some alveolar spaces were slightly widened, and there was bleeding in the alveolar cavity; in the sodium valproate group, partial fibrosis of alveolar wall was observed in the lung tissue, and the pathological changes were lighter than those in the simple scald+ saline group. At 24 h after scald injury, alveolar edema, widened pulmonary septum, and increased inflammatory cell infiltration were observed in the lung tissues of rats in the simple scald+ saline group, with obvious fibrosis of alveolar wall, accompanied by a large number of inflammatory cell infiltration, and the formation of pulmonary bullae was observed; in the sodium valproate group, the connective tissue of alveolar septum proliferated, the alveolar septum widened significantly, and the lesion was lighter than that in the simple scald+ saline group. At 6 h after scald, the Ahshcroft fibrosis score and lung injury score in sodium valproate group were (5.24±0.07) and (5.83±0.05) points, respectively, which were significantly lower than those in simple scald + saline group [(6.12±0.06) and (6.73±0.05) points], the differences between the 2 groups were statistically significant (t= 2.176, 2.467; P<0.05); at 24 h after scald, the Ahshcroft fibrosis score and lung injury score in sodium valproate group were (5.31±0.06) and (8.13±0.07) points, respectively, which were significantly lower than those in simple scald + saline group [(6.81±0.07) and (9.02±0.08) points], the differences between the 2 groups were statistically significant (t=2.597, 2.917; P<0.05).
Conclusion Sodium valproate can reduce the level of inflammatory factors in lung tissue of 50% TBSA Ⅲ degree scald shock rats, inhibit the increase of pulmonary vascular permeability, reduce the moisture content of lung tissue, reduce the degree of pulmonary fibrosis, and significantly reduce the degree of lung injury, which has potential application value in the early treatment of burn shock.
Key words:
Lung,
Burns,
Rats,
Sodium valproate,
Inflammatory factor,
Vascular permeability
Meidi Zhu, Shuming Wang, Sijia Guo, Weibin Jing, Mingming Ma, Rui Liu. Protective effect of sodium valproate on lung function in rats with 50% total body surface area Ⅲ degree scalded injury[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2023, 18(01): 47-52.