Salidroside pretreatment alleviates PM2.5 caused lung injury via inhibition of apoptosis and pyroptosis through regulating NLRP3 Inflammasome.

Abstract

Ambient fine particulate matter (PM2.5) is considered a leading cause of pathogenic particulate matter induced lung injury. And Salidroside (Sal), the major bioactive constituent isolated from Rhodiola rosea L., has been shown to ameliorate lung injury in various conditions. To uncover the possible therapy for PM2.5 related pulmonary disease, we evaluated the protective role of Sal pre-treatment on PM2.5 induced lung injury in mice by utilizing the survival analysis, hematoxylin and eosin (H&E) staining, lung injury score, lung wet-to-dry weight ratio, enzyme-linked immunosorbent assay (ELISA) kits, immunoblot, immunofluorescence, and transmission electron microscopy (TEM). Impressively, our findings strongly indicated Sal as an effective precaution against PM2.5 induced lung injury. Pre-administration of Sal before PM2.5 treatment reduced the mortality within 120h and alleviated inflammatory responses by reducing the release of proinflammatory cytokines, including TNF-α, IL-1β, and IL-18. Meanwhile, Sal pretreatment blocked apoptosis and pyroptosis that introduced the tissue damage under PM2.5 treatment via regulating Bax/Bcl-2/caspase-3 and NF-κB/NLRP3/caspase-1 signal pathways. In summary, our research demonstrated that Sal could be a potential preventative therapy for PM2.5 caused lung injury by inhibiting the initiation and development of apoptosis and pyroptosis through down-regulating NLRP3 inflammasome pathway.