Background  Diffuse interstitial and alveolar edema caused by oxidative stress and inflammation are the main factors leading to acute lung injury (ALI). Short chain fatty acids (SCFAs), especially sodium propionate (SP), have antioxidant and anti-inflammatory effects.

  Objective  To investigate the effect of SP on oxidative stress and inflammation in rats with ALI induced by lipopolysaccharide (LPS).

  Methods  Male SD rats were randomly divided into model group, low-dose SP group, high-dose SP group, and control group, with 5 rats in each group. Rats in low-dose SP group and high-dose SP group were given 300 mg/kg and 500 mg/kg of SP by gavage, respectively. The model group and the control group were given the same amount of normal saline by gavage. After continuous gavage for 1 week, intratracheal infusion of LPS was used to establish ALI model. At 6 hours after modeling, the partial blood oxygen pressure (PaO₂) of abdominal aorta and wet/dry weight (W/D) of lung tissue were determined. HE staining was used to observe lung tissue pathological changes, ELISA method was used to determine the concentration of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 10 (IL-10) in serum and alveolar lavage fluid (BALF). Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in lung tissue were also detected, and Western blot method was used to detect the expression levels of NF-κB p65, p-NF-κB p65, Keap1, Nrf2 protein in lung tissue.

  Results  Compared with the control group, the lung injury in model group was obvious. The W/D value, MDA content and the expression of P-NF-κB P65 and Keap1 protein in lung tissue increased (all P＜0.05), and the TNF-α, IL-6 and IL-10 in serum and BALF also increased (all P＜0.05), while the PaO₂ in arterial blood, the activity of SOD and the Nrf2 protein expression in lung tissue decreased (all P＜0.05). Compared with the model group, the lung injury in SP group was less. The W/D value, MDA content and the expression of P-NF-κB P65 and Keap1 protein in lung tissue decreased (all P＜0.05), the TNF-α, IL-6 content in serum and BALF also decreased (all P＜0.05), while the PaO₂ in arterial blood, the IL-10 in serum and BALF, and the SOD activity, Nrf2 protein expression in lung tissue increased (all P＜0.05). The above changes were more obvious in the high-dose SP group than those in the low-dose SP group (all P＜0.05).

  Conclusion  SP can reduce LPS-induced ALI in rats by regulating the Keap1/Nrf2 signaling pathway and inhibiting the activation of NF-κB signaling pathway, thereby reducing oxidative stress injury and inflammatory response.