Combined transcriptomic and proteomic analysis reveals the mechanism of Xing-Qi-Huo-Xue granules on BLM-induced pulmonary fibrosis in rats

Abstract Background Pulmonary fibrosis is a phenotype of many lung disease pathologies, characterized by alveolar structure destruction, extracellular matrix anomalous accumulation, and abnormal collagen deposition. Traditional Chinese medicine is becoming increasingly important in treating pulmonary fibrosis, and Xing-Qi-Huo-Xue (XQHX) granules have been clinically proven effective, but the underlying mechanism is unclear. Purpose In this experiment, The mechanism of XQHX in treating rats with PF was elucidated by combined transcriptomic and proteomic analyses. Method The main components of XQHX granules was detected by liquid chromatography/mass spectrometry (LC/MS) first. A bleomycin (BLM)-induced rat model was established and lung histology was assessed by hematoxylin eosin and Masson's stain. Rat lung tissues were subjected to transcriptome and proteome sequencing, and bioinformatic analyses of differential genes/proteins were performed. Collagen I/III mRNA expression levels were determined by RT-qPCR, and lung hydroxyproline (HYP) levels were determined by colorimetric assay. Results A total of 16 main compounds including agroastragaloside IV, astragaloside I, astragaloside II, etc. in XQHX were detected by LC/MS. XQHX significantly improved BLM-induced lung tissue structure destruction and HYP content. Furthermore, XQHX inhibited lung tissue mRNA expression of collagens I, and III. Bioinformatics analysis showed that 1657 genes and 590 proteins were differentially expressed in the normal control group (N) compared to the BLM-induced control group (P), and 2.46 g/kg XQHX- treated group (X) had 805 genes and 499 proteins differentially expressed. Then we identified that XQHX exerts an anti-fibrotic effect by regulating arginine (Arg1), which is involved in the arginine biosynthesis pathway and the arginine and proline metabolism pathway. Conclusion Our results suggest that XQHX reduces arginase biosynthesis by down-regulating Arg1 expression as a central mechanism and potential therapeutic approach to prevent BLM-induced pulmonary fibrosis.