[Mechanism of traditional Chinese medicine Xinfeng Capsules in improving pulmonary interstitial lesions in adjuvant arthritis model rats based on lncRNA-mediated "sponging" of miR155 to regulate Notch-RBP-Jκ signaling pathway].

This study aimed to investigate the mechanism by which Xinfeng Capsules(XFC), a traditional Chinese medicine preparation, ameliorates interstitial lung disease(ILD) in adjuvant arthritis(AA) model rats. It exerts the effect by regulating the adsorption of microRNA155(miR155) by metastasis-associated lung adenocarcinoma transcript 1(MALAT1), thereby ameliorating the abnormal expression of miR155 and subsequently modulating the neurogenic locus Notch homolog protein(Notch)-recombination signal binding protein for immunoglobulin kappa J region(RBP-Jκ) signaling pathway. An AA rat model was established, and after intragastric administration of XFC, pharmacodynamic evaluation was conducted on rats in each group, including arthritis index scoring, paw swelling measurement, pulmonary function test, and histopathological examinations of lung tissue and ankle joint synovium. ELISA was used to detect the levels of related inflammatory cytokines. RT-qPCR was performed to determine the expression levels of long non-coding RNA(lncRNA) MALAT1, miR155 and genes related to the Notch-RBP-Jκ signaling pathway, while Western blot was applied to examine the protein expression of ETS transcription factor-1(ETS-1) and RBP-Jκ. The results showed that, compared with the model group, XFC significantly improved pulmonary function, alleviated paw swelling, and inhibited fibrous hyperplasia and inflammatory cell infiltration in synovial and lung tissue of AA rats. It also reduced the serum levels of pro-inflammatory cytokines such as tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6), thereby alleviating the systemic inflammatory responses. In addition, XFC ameliorated the aberrant expression of lncRNA MALAT1 and miR155, inhibited the transcription of Notch homolog 1(Notch1), Jagged canonical Notch ligand 1(Jagged1), nuclear factor of activated T cells cytoplasmic 1(NFATC1) and interferon regulatory factor 8(IRF8), and further promoted the protein expression of ETS-1 while suppressing RBP-Jκ protein expression. In summary, XFC may exert its effects by enhancing the roles of lncRNA MALAT1 as a molecular sponge to adsorb miR155, thereby inhibiting the aberrant expression of miR155, which in turn modulates the overactivation and transcription of the Notch-RBP-Jκ signaling pathway, suppresses the articular inflammatory response and ameliorates ILD lesions in AA rats.