To observe the regulatory mechanism of Yupingfeng Powder (玉屏风散) on “activation of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway inhibiting fibroblast autophagy in pulmonary fibrosis”, and to explore the mechanism of Yupingfeng Powder in improving idiopathic pulmonary fibrosis (IPF).

Forty-eight Sprague Dawley (SD) rats were randomly divided into 8 groups with 6 rats in each, including blank group, sham-operated group, model group, positive control (prednisone) group, STAT3 inhibitor (sorafenib) group and Yupingfeng Powder high, middle and low dose groups. The rats in the model group and in each administration group were injected with bleomycin (BLM) intratracheally to establish the lung fibrosis model. Gastric administration was started after the 14th day of modeling, and prednisone [6 mg/ (kg·d)]was given to the positive control group, sorafenib[30 mg/ (kg·d)]was given to the STAT3 inhibitor group, and Yupingfeng Powder solution was given to the high dose group[6 g/ (kg·d)], the middle dose group[3 g/ (kg·d)]and the low dose group[1.5 g/ (kg·d)], respectively. The equal volume of saline was given to the blank group and the model group. The drug was continuously administered until the 30th day. The symptoms and signs, the changes in lung tissue morphology, the α-smooth muscle actin (α-SMA) protein expression, the levels of interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1), JAK2/STAT3 signaling pathway and respective phagocytosis index in lung tissues were observed before and after treatment.

Compared with the blank and sham-operated groups, the model group showed severe symptoms, signs and lung tissue injury status, significantly higher levels of IL-6 andTGF-β1 (P<0.01), significantly higher expressions of α-SMA, JAK2, phosphorylated Janus kinase 2 (p-JAK2), STAT3, phosphorylation signal transducer and activator of transcription 3 (p-STAT3) proteins (P<0.01) and myeloid cell leukemia 1 (Mcl-1) protein and mRNA (P<0.01). The protein and mRNA expressions of Beclin1, phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) and Atg14 were significantly reduced (P<0.01), the binding between Beclin1 and Mcl-1 was significantly enhanced, and fibroblast autophagy was significantly reduced. After treatment, compared with those in the model group, all the indexes of the rats in the high and middle dose groups of Yupingfeng Powder, prednisone group and sorafenib group were significantly improved (P<0.01 or P<0.05), the binding between Beclin1 and Mcl-1 was significantly weakened, and the autophagy of fibroblasts was significantly increased, while the indicators of the low dose group basically showed no significant changes. Overall, the efficacy of the high dose group of Yupingfeng Powder was better than that of the middle and low dose groups, and equal to that of the prednisone group and close to that of the sorafenib group.

Yupingfeng Powder is able to reduce collagen fiber deposition by increasing fibroblast autophagy to inhibit pulmonary fibrosis, and this process may be related to the inhibition of the phosphorylation and activation of the JAK2/STAT3 pathway by decreasing the levels of IL-6 and TGF-β1, thus blocking the binding of Mcl-1 to Beclin1, further increasing the formation of type Ⅲ PI3K complex, and enhancing the ability of Beclinl to activate autophagy.