Abstract
OBJECTIVE: To investigate how Srolo Bzhtang (SBT), a classical Tibetan medicine formula, improves oxidative stress and ultimately alleviates pulmonary fibrosis in rats through the Nrf2/HO-1 and PI3K/AKT/mTOR pathways. METHODS: Seventy-two SD rats were randomly assigned to 12 sham surgery groups (Sham group, receiving equal volumes of normal saline) and 60 model groups (established by intratracheal instillation of bleomycin to induce pulmonary fibrosis). Twenty-four hours after modeling, the model groups were randomly divided into the model group (Model), the positive drug group (pirfenidone, 150 mg/kg), and low, medium, and high dose Soroxisol groups (SBT-L 0.5 g/kg, SBT-M 1.5 g/kg, SBT-H 4.5 g/kg), with 12 rats in each group. Each group received the drug by gavage once daily for 21 days.The Sham and Model groups received equal volumes of normal saline. HE and Masson staining were used to observe the pathological changes of pulmonary fibrosis in each group. ELISA was used to measure the levels of inflammatory factors (TNF-α, IL-8) and matrix metalloproteinases (MMP-2, MMP-9) in serum. The activities of malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were also measured. The expression levels of Nrf2/HO-1 and proteins in the PI3K/AKT/mTOR signaling pathway in lung tissue were determined by Western blot. RESULTS: HE and Masson staining showed that pulmonary fibrosis was more severe in the Model group than in the Sham group, and each drug administration group could reverse this process to varying degrees. SBT inhibited the levels of inflammatory factors TNF-α and IL-8 (all P < 0.05), and compared with the Model group, the levels of matrix metalloproteinases MMP-2 and MMP-9 were decreased (all P < 0.05). Pathological section results showed that SBT improved lung tissue damage in pulmonary fibrosis rats to some extent. Compared with the Model group, MDA levels in the low-, medium-, and high-dose SBT groups decreased (all P < 0.05), and SOD enzyme activity showed an increasing trend. Western blot results indicated that, compared with the Model group, the low-, medium-, and high-dose SBT groups activated the protein expression of Nrf2 and HO-1 (all P < 0.05) and downregulated the expression levels of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR (all P < 0.05). CONCLUSION: SBT affects the Nrf2/HO-1 and PI3K/AKT/mTOR signaling pathways, inhibits oxidative stress, and thereby delays the progression of pulmonary fibrosis in rats.