Effect Of Trollius Altaicus Flavonoids On The Prevention And Treatment Of Pulmonary Fibrosis Induced By PM_2.5 In Rats

Objective:To study the effect of Trollius Altaicus Flavonoids（TAF）on the prevention and treatment of PM_2.5 induced pulmonary fibrosis in rats,laying a foundation for its medicinal development.Methods:60 wistar rats of SPF grade,with a body mass of 200±20g,were randomly divided into 6 groups:normal control group,PM_2.5 model group,PM_2.5+low,medium and high dose of TAF（125,250,500mg/kg·bw）,PM_2.5+dexamethasone positive control group（0.2mg/kg·bw）,10 rats in each group.In addition to the normal control group and the model group,each dose group and the positive control group were given the test drug once a day for 28 days.In addition to the normal control group,PM_2.5 suspension（50mg/kg·bw）was infused into the trachea twice a week for four weeks,eight times in total.29 d,blood samples were collected from abdominal aorta,and the whole blood was collected for leukocyte classification and counting.Serum samples were collected to detect lactate dehydrogenase（LDH）,superoxide dismutase（SOD）,glutathione（GSH）,malondialdehyde（MDA）,nitric oxide（NO）,interleukin-10（IL-10）,interleukin-1β（IL-1β）,tumor necrosis factor-α（TNF-α）,hydroxyproline（HYP）,pre type I The contents of collagen amino terminal peptide（PINP）and procollagen typeⅢamino terminal peptide（PⅢNP）were measured.The left lung of rats was taken for alveolar lavage,and BALF was collected.The contents of IL-10,IL-1β,TNF-α,HYP,PINP and PⅢNP were detected.The right upper lobe of rats was taken for pathological histology examination,and the wet/dry mass ratio（W/D）of lung was calculated after weighing the lower lobe.Results:Compared with normal control group,model group rats peripheral blood leukocyte count,serum and BALF IL-1β,TNF-α,HYP,PINP,PⅢNP content increased（P<0.01）,serum LDH,MDA,NO levels increased（P<0.01）,W/D increased lung tissue（P<0.01）,IL-10,SOD and GSH content lower（P<0.01）;The results of histopathological examination showed that in the model group,large areas of consolidation,edema,hemorrhage,destruction of alveolar structure,infiltration of pulmonary interstitial inflammatory cells,a large number of dust nodules and deposition of bright blue collagen fibers were found.Compared with model group,TAF 250,500 mg/kg group of rat peripheral blood leukocyte count,serum and BALF IL-1βand TNF-αwere decreased（P<0.05 or P<0.01）,serum LDH,MDA and NO were decreased（P<0.05 or P<0.01）,W/D reduce the lung tissue（P<0.05 or P<0.01）,IL-10,SOD and GSH content increased（P<0.05 or P<0.01）;There was no significant difference between the high dose group and the dexamethasone positive control group.The results of pathological examination showed that with the increase of total flavonoid intervention dose,the damage of lung tissue morphology and structure decreased,lung consolidation,dust nodule,inflammatory cell infiltration and collagen deposition decreased.In the TAF500 mg/kg group,a small number of inflammatory cells infiltrated and collagen fibers deposited in the lung,and the destruction area of alveoli and bronchi was small,similar to that of dexamethasone group.Conclusions:The trollius altaicus flavonoids had a certain effect on the prevention and treatment of pulmonary fibrosis induced by PM_2.5 in rats.