Astragaloside IV pre-treatment attenuates PM2.5-induced lung injury in rats: Impact on autophagy, apoptosis and inflammation.

ABSTRACT

BACKGROUND: Fine particulate matter (PM2.5) with an aerodynamic diameter of less than 2.5 µm, exerts serious lung toxicity. At present, effective prevention measures and treatment modalities for pulmonary toxicity caused by PM2.5 are lacking. Astragaloside IV (AS-IV) is a natural product that has received increasing attention from researchers for its unique biological functions. PURPOSE: To investigate the protective effects of AS-IV on PM2.5-induced pulmonary toxicity and identify its potential mechanisms. METHODS: The rat model of PM2.5-induced lung toxicity was created by intratracheal instillation of PM2.5 dust suspension. The investigation was performed with AS-IV or in combination with autophagic flux inhibitor (Chloroquine) or AMP-sensitive protein kinase (AMPK)-specific inhibitor (Compound C). Apoptosis was detected by terminal deoxy-nucleotidyl transferase dUTP nick end labeling (TUNEL) and western blotting. Autophagy was detected by immunofluorescence staining, autophagic flux measurement, western blotting, and transmission electron microscopy. The AMPK/mTOR pathway was analyzed by western blotting. Inflammation was analyzed by western blotting and suspension array. RESULTS: AS-IV prevented histopathological injury, inflammation, autophagy dysfunction, apoptosis, and changes in AMPK levels induced by PM2.5. AS-IV increased autophagic flux and inhibited apoptosis and inflammation by activating the AMPK/ mammalian target of rapamycin (mTOR) pathway. However, AS-IV had no protective effect on PM2.5-induced lung injury following treatment with Compound C or Chloroquine. CONCLUSION: AS-IV prevented PM2.5-induced lung toxicity by restoring the balance among autophagy, apoptosis, and inflammation in rats by activating the AMPK/mTOR signaling pathway.