Tetrahydropalmatine protects against acute lung injury induced by limb ischemia/reperfusion through restoring PI3K/AKT/mTOR-mediated autophagy in rats

Background: Limb ischemia/reperfusion (I/R) is a common clinical process that frequently induces acute lung injury (ALI). Tetrahydropalmatine (THP) is a major bioactive constituent of various traditional Chinese medicine with protective effects on inflammation and oxidation. In this study, we aimed to investigate the possible protective effect of THP on ALI induced by limb I/R.

Methods: Rats were used to establish ALI through limb I/R. After administration of three doses of THP, the lung injury was evaluated by hematoxylin-eosin staining, tissue wet/dry weight ratio and ELISA examination of myeloperoxidase (MPO), malondialdehyde (MDA) and Super Oxide Dismutase (SOD). Additionally, PI3K/AKT/mTOR pathway and autophagy markers were determined by Western blot. To confirm the role of autophagy in the effect of THP on ALI, 3-methyladenine (3-MA), THP or THP + rapamycin (RAPA) was given to the model rats, and then evaluated the parameters above mentioned.

Results: The pulmonary histological lesions and wet/dry were significantly induced after limb I/R. Concurrently, I/R significantly increased MPO and MDA, and decreased SOD in lung tissues. These changes were reversed after THP treatment. Additionally, THP exerted inhibitory effect on the I/R-induced decrease of phosphorylation of PI3K/AKT/mTOR and increase of autophagy activity. The effects by THP on lung injury, PI3K/AKT/mTOR signaling and autophagy were also observed after treatment with 3-MA, an autophagy inhibitor, whereas were blocked by combinational treatment with RAPA, an autophagy inducer.

Conclusion: Our data suggested that THP had significant protection against ALI and this might be achieved by autophagy inhibition through rescuing PI3K/AKT/mTOR activity.