To investigate the protective effects and potential mechanisms of 6-gingerol against acute respiratory distress syndrome (ARDS) in juvenile mice through nerve growth factor-induced clone B (Nur77).

The juvenile mouse model of ARDS was established by tracheal instillation of lipopolysaccharide. After modeling, 48 juvenile mice were randomly divided into the model group, the 6-gingerol group (intraperitoneal injection of 30 mg·kg^-1 6-gingerol), the 6-gingerol+sh-NC group (intranasal instillation of sh-NC negative control adenovirus+intraperitoneal injection of 30 mg·kg^-1 6-gingerol), and the 6-gingerol+sh-Nur77 group (intranasal instillation of sh-Nur77 adenovirus+intraperitoneal injection of 30 mg·kg^-1 6-gingerol). Another 12 normal juvenile mice were given an equal volume of sterile 0.9% NaCl by tracheal instillation as the sham operation group. Detected the lung wet/dry (W/D) ratio of young mice in each group. The immunohistochemistry method was used to detect the positive expression of collagen Ⅲ in lung tissues. The kit was used to detect apoptosis in the lung tissues of young mice. The expressions of pathway-related proteins were detected by Western blotting.

The W/D ratios of the sham operation group, the model group, the 6-gingerol group, the 6-gingerol+sh-NC group and the 6-gingerol+sh-Nur77 group were 2.20±0.26, 6.65±0.92, 3.89±0.52, 3.72±0.44 and 5.55±0.78, respectively; the positive levels of collagen Ⅲ were 1.00±0.22, 3.99±0.54, 1.85±0.28, 1.76±0.29 and 2.79±0.34, respectively; the apoptosis rates were (4.65±0.66)%, (39.62±5.03)%, (18.63±2.33)%, (17.82±2.12)% and (33.65±5.03)%, respectively; the levels of phosphorylated phosphatidylinositol 3-kinase/phosphatidylinositol 3-kinase (p-PI3K/PI3K) were 1.00±0.13, 1.66±0.22, 1.23±0.17, 1.21±0.14 and 1.58±0.24, respectively; the levels of phosphorylated protein kinase B/protein kinase B (p-Akt/Akt) were 1.00±0.16, 1.78±0.26, 1.33±0.21, 1.38±0.19 and 1.60±0.22, respectively. Compared with the sham operation group, the differences in the above indicators of the model group were statistically significant (all P<0.05); compared with the model group, the differences in the 6-gingerol group were statistically significant (all P<0.05); compared with the 6-gingerol+sh-NC group, the differences in the 6-gingerol+sh-Nur77 group were also statistically significant (all P<0.05).

6-gingerol intervention can improve lung injury in young ARDS mice, up-regulate the expression of Nur77, inhibit lung tissue inflammatory response, reduce lung tissue apoptosis, and promote coagulation/fibrinolytic balance, and its mechanism of action may be related to the inhibition of PI3K/Akt pathway.