[Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma alleviates acute lung injury in rats by regulating autophagy via PI3K/Akt/mTOR pathway].

ABSTRACT

This study aims to reveal the effects of the herb pair Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma(AR-SMRR) on phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR) pathway and autophagy in the lung tissue of the rat model of acute lung injury(ALI). Fifty adult male SD rats were randomized into sham, model, autophagy inhibition(intraperitoneal injection of chloroquine at 10 mg·kg~(-1)), autophagy induction(intraperitoneal injection of rapamycin at 15 mg·kg~(-1)), and AR-SMRR(5 g·kg~(-1), gavage) groups. The rats in the sham group received intratracheal instillation of normal saline, and those in other groups received intratracheal instillation of lipopolysaccharide(LPS, 5 mg·kg~(-1)) for the modeling of ALI. Seven days before the operation, the rats in the sham and model groups were administrated with normal saline, and those in other groups with corresponding drugs. Specimens were collected 24 h after modeling. The pathological changes of the lung tissue were observed under a light microscope. The lung wet/dry weight ratio and the lactate dehydrogenase(LDH) activity and total protein concentration in the bronchoalveolar lavage fluid(BALF) were measured. Western blot was employed to measure the protein levels of microtubule-associated protein 1-light chain 3(LC3), beclin-1, p62, PI3K, Akt, and mTOR. Compared with the sham group, the model group showed increased histopathological score of the lung tissue, lung wet/dry weight ratio, and LDH activity and protein concentration in BALF. Autophagy inhibition further increased these indicators compared with the model group, while autophagy induction and AR-SMRR lowered the levels. In addition, AR-SMRR up-regulated the protein levels of LC3-Ⅱ and beclin-1, down-regulated the expression of p62, and inhibited the expression of p-PI3K, p-Akt, and p-mTOR in the lung tissue of ALI rats. The findings suggest that AR-SMRR can alleviate the lung injury and edema in the rat model of ALI induced by LPS by enhancing autophagy via down-regulating PI3K/Akt/mTOR signaling pathway.