Abstract
Pterostilbene (PTER) is a kind of stilbene compound with biological activity isolated from plants such as red sandalwood, blueberry and grape. It has anti-tumor, anti-bacterial, anti-oxidation and other pharmacological activities. However, the underlying mechanism of the protective effect of PTER on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remained not clarified. In this study, LPS was used to establish a mouse model of ALI. Bronchoalveolar lavage fluid (BALF) was collected for inflammatory cells, and the wet-to-dry weight ratio of the lungs was measured. The activities of myeloperoxidase (MPO), antioxidant indexes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and oxidation index such as malondialdehyde (MDA) in lung tissues of mice were measured by the corresponding kits. The levels of Cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), TNF-α, IL-6 and IL-1β in lung tissues of mice were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The activities of Nrf2, HO-1, p-p65 and p-IκB were determined by western blotting. The results showed that the model of LPS-induced ALI was successfully replicated, and it was found that PTER could significantly improve the pathological degree of ALI such as sustained the integrity of the lung tissue structure, alleviated pulmonary interstitial edema and alveolar wall thickening, reduced infiltrated inflammatory cells. PTER could decrease the number of inflammatory cells and obviously inhibit the increase of W/D ratio caused by LPS. PTER could also significantly reduce LPS-induced MPO and MDA, and increase LPS-decreased SOD, CAT and GSH-Px in the lungs. In addition, it was also found that PTER has the ability to decrease LPS-induced production of COX-2, iNOS, TNF-α, IL-6 and IL-1β. The underlying mechanism involved in the protective effect of PTER on ALI were via activating Nrf2 and HO-1, and inhibiting the phosphorylation of p65 and IκB. These results suggested that PTER can protect LPS-induced ALI in mice by inhibiting inflammatory response and oxidative stress, which provided evidence that PTER may be a potential therapeutic candidate for LPS-induced ALI intervention.
Highlights
Acute lung injury (ALI) is a respiratory disease characterized by a large number of inflammatory cell infiltration, damage to alveolar epithelial cells and capillary endothelial cells, destruction of alveolar structure, pulmonary interstitial edema, marked thickening of alveolar walls, and acute hypoxic respiratory insufficiency
In order to confirm the effect of PTER on inflammatory cells in Bronchoalveolar lavage fluid (BALF) with LPS-induced acute lung injury (ALI), BALF was collected to count the number of total cells, neutrophils and macrophages
The number of total cells (Figure 2A), neutrophils (Figure 2B), and macrophages (Figure 2C) in BALF in the LPS-induced model group increased significantly, while PTER pretreatment reduced the infiltration of these inflammatory cells into the lung tissue
Summary
Acute lung injury (ALI) is a respiratory disease characterized by a large number of inflammatory cell infiltration, damage to alveolar epithelial cells and capillary endothelial cells, destruction of alveolar structure, pulmonary interstitial edema, marked thickening of alveolar walls, and acute hypoxic respiratory insufficiency. Respiratory support technology (mainly including: small tidal volume ventilation, positive end expiratory pressure, prone position ventilation, high frequency oscillatory ventilation, extracorporeal lung membrane technology and so on) is currently the most important treatment for ALI in clinical practice (Amato et al, 1998). Some drugs, such as glucocorticoids and ulinastatin, have therapeutic effects on ALI, but they are not widely recommended in clinic due to more adverse reactions (Liu et al, 2013). The morbidity and mortality of livestock and poultry remain high, causing significant economic losses to the livestock industry, and seriously hindering the development of the livestock industry
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