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. 2024 Nov;14(11):286.
doi: 10.1007/s13205-024-04130-3. Epub 2024 Oct 30.

Sodium propionate ameliorates lipopolysaccharide-induced acute respiratory distress syndrome in rats via the PI3K/AKT/mTOR signaling pathway

Fang He #  1   2   3 , Jiang-Shan Zhong #  1   2   3 , Chun-Lan Chen  1   2   3 , Peng Tian  1   2   3 , Jie Chen  1   2   3 , Xian-Ming Fan  1   2   3
Affiliations

Sodium propionate ameliorates lipopolysaccharide-induced acute respiratory distress syndrome in rats via the PI3K/AKT/mTOR signaling pathway

Fang He et al. 3 Biotech. 2024 Nov.

Abstract

Acute respiratory distress syndrome (ARDS) is a severe lung disease characterized by significant hypoxemia, which impairs the oxygen supply necessary for optimal lung function. This study aimed to investigate the effects of sodium propionate (SP), the primary end product of intestinal flora fermentation of dietary fiber, on lipopolysaccharide (LPS)-induced ARDS in rats. The rats were treated with SP, after which the lung wet/dry ratio, arterial partial oxygen pressure (PaO2), levels of pro- and anti-inflammatory cytokines, tight junction proteins ZO-1 and Occludin, as well as LC3 and phosphorylated PI3K (p-PI3K)/p-AKT/p-mTOR protein levels, were measured. Additionally, histopathological analysis was conducted. The results indicated that SP effectively alleviated arterial hypoxemia in rats and mitigated the pathological damage to both intestinal and lung tissues caused by LPS. Notably, SP significantly reduced the levels of inflammatory factors TNF-α and IL-6 in the blood and bronchoalveolar lavage fluid (BALF) of ARDS rats, while increasing the concentration of the anti-inflammatory factor IL-10. Furthermore, SP inhibited the activation of the PI3K/AKT/mTOR signaling pathway and enhanced the LC3II/LC3I ratio in lung tissue. Therefore, SP may improve LPS-induced ARDS in rats by inhibiting the activation of the PI3K/AKT/mTOR signaling pathway, promoting autophagy, decreasing the production and release of inflammatory markers, and reducing alveolar epithelial damage.

Keywords: Acute respiratory distress syndrome; PI3K/AKT/mTOR signaling pathway; Short-chain fatty acids; Sodium propionate.

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Conflict of interest statement

Conflict of interestThe authors declare that they have no conflict of interest in the publication.

Figures

Fig. 1
Fig. 1
SP ameliorated hypoxemia and lung injury in ARDS rats. A Lung wet/dry weight ratio in rats. B Arterial partial oxygen pressure (PaO2) in rats. C Pathological score of lung injury in rats. D HE staining of lung tissue in rats (×200). For all bar graphs, data are mean ± SD, ****p < 0.0001, as compared with Control, and #p < 0.05, ##p < 0.01, ####p < 0.0001, as compared with ARDS
Fig. 2
Fig. 2
SP effectively suppressed both systemic and local lung inflammation in ARDS rats. A TNF-α concentration in bronchoalveolar lavage fluid (BALF) of rats. B IL-6 concentration in BALF of rats. C IL-10 concentration in BALF of rats. D TNF-α concentration in serum of rats. E IL-6 concentration in serum of rats. F IL-10 concentration in serum of rats. For all bar graphs, data are mean ± SD, **p < 0.01, ***p < 0.001, ****p < 0.0001, as compared with Control, and #p < 0.05, ##p < 0.01, ####p < 0.0001, as compared with ARDS
Fig. 3
Fig. 3
SP inhibited the activation of the PI3K/AKT/mTOR signaling pathway and promoted autophagy in ARDS rats. A Western-blot was used to evaluate the expression of p-PI3K, p-AKT, p-mTOR and LC3 in lung tissue of rats. B The relative intensity of p-PI3K protein bans normalized to GAPDH band. C The relative intensity of p-AKT protein bans normalized to GAPDH band. D The relative intensity of p-mTOR protein bans normalized to GAPDH band. E The intensity ratio of LC3 II band to LC3I band. For all bar graphs, data are mean ± SD, **p < 0.01, ****p < 0.0001, as compared with Control, and ##p < 0.01, ####p < 0.0001, as compared with ARDS
Fig. 4
Fig. 4
SP ameliorated intestinal injury and preserved intestinal mucosal integrity in ARDS rats. A HE staining of intestinal tissue in rats (×200). B Pathological score of intestinal injury in rats. C ZO-1 integral optical density (IOD) in intestinal tissue of rats. D Occludin integral optical density (IOD) in intestinal tissue of rats. E IHC staining of ZO-1 in intestinal tissue of rats. F IHC staining of Occludin in intestinal tissue of rats. For all bar graphs, data are mean ± SD, ****p < 0.0001, as compared with Control, and ####p < 0.0001, as compared with ARDS
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