Effects of Tripterygium wilfordii polyglycosides on a rat model of pulmonary fibrosis via miR-146/NF-κB signaling pathway
AIM To investigate the role of Tripterygium wilfordii polyglycosides as an inhibitor of pulmonary fibrosis progression in rats.METHODS In contrast to the six rats randomly selected into the blank group,another 34 rats were induced into a rat model of pulmonary fibrosis by bleomycin sulfate ( 5 mg/mL) injection using tracheal puncture followed by 7 days later random assignment of the survival thirty rats into the model group,the prednisone acetate group (1.17 mg/kg) and the low,medium and high dose tripterygium wilfordii polyglycosides groups (1,3,6 mg/kg) for 21 days corresponding dosing of the drugs.The general characteristics of rats were observed during administration.After the administration,the rats had their pulmonary morphology observed;their lung coefficients of each group compared;their structural changes of lung tissue observed using HE staining;their collagen deposition observed by Masson staining;and their hyperplastic conditions assessed by the criteria for judging pulmonary fibrous hyperplasia;their serum HYP,TNF-α,IL-1β and IL-6 levels detected by ELISA;their pulmonary expressions of miR-146a,NF-κB and Col-I mRNA detected by RT-qPCR method;and their pulmonary protein expressions of p-P65,IRAK1,TRAF6 and α-SMA detected by Western blot.RESULTS Compared with the blank group,the model group displayed increased levels of serum TNF-α,IL-6,IL-1β and HYP ( P<0.01);decreased pulmonary miR-146a mRNA expression ( P<0.01);and increased expressions of NF-κB,Col-I mRNA and p-P65,IRAK1,TRAF6 and α-SMA protein ( P<0.01 ).Compared with the model group,the groups intervened with either prednisone acetate or Tripterygium wilfordii polyglycoside shared differently improved alveolar structure and inflammatory cell infiltration;reduced fibrosis;increased pulmonary miR-146a mRNA expression ( P<0.01);increased levels of TRAF6-α,IL-6,IL-1β and HYP in serum,and expressions of NF-κB and Col-I mRNA and expression of p-P65,IRAK1,TRAF6 and α-SMA protein of the lung tissue ( P<0.05,P<0.01) as well.CONCLUSION Tripterygium wilfordii polyglycosides can delay the progression of pulmonary fibrosis in rats,and its mechanism may be related to the regulation via miR-146/NF-κB signaling pathway.