Objective To investigate the intervention effects of Yangqing Chenfei Fang (YCF), Baojin Chenfei Fang (BCF), and Jinshui Chenfei Fang (JCF) at different pathological stages of silicosis in a rat model. Methods A total of 216 specific pathogen free rats were randomly divided into control group, silicosis group, tetrandrine group, YCF group, BCF group and JCF group, with 35-36 rats in each group (11-12 rats at each time point). The rats in control group were treated with intragastric administration of pure water [administration volume at 2.5 mL/(kg·time)], while the rats of other five groups were treated with silica suspension at 250 mg/kg body weight to induce a silicosis model using the one-time non-exposed tracheal method. Intragastric administration of the corresponding drugs was performed at three time points at days 1-14 (early stage of silicosis), days 15-28 (middle stage of silicosis), and days 29-42 (late stage of silicosis) after modeling. Pulmonary function enhanced pause (Penh), forced vital capacity (FVC), and dynamic lung compliance (Cdyn) of rats in the six groups was assessed on days 15, 29, and 43 after modeling. Histopathological changes in lung tissues were observed, and relative expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, hydroxyproline, collagenⅠ(COL-Ⅰ), and α-smooth muscle actin (α-SMA) were detected in lung tissues. Results i) Pulmonary function index. The index of Penh in three stages of silicosis of rats in YCF group, BCF group and JCF group was lower than that in the silicosis group at the same stage (all P<0.05), and the index of Penh was higher than that in the tetrandrine group at the same stage (all P<0.05). The index of FVC of rats in YCF group, BCF group and JCF group at the middle stage was higher than that in the silicosis group at the same stage (all P<0.05), as well as the index of Cdyn was higher than that in the tetrandrine group at the same stage (all P<0.05). ii) Histopathology of lung tissue. Rats of the silicosis group exhibited alveolitis, fibro stripe, and collagen deposition in lung tissues in the early stage compared with rat of the control group, with fibrosis progressively worsening over time and inflammation persisting throughout the disease course. Pathological changes of lung tissues were alleviated to varying degrees in the tetrandrine groups, YCF group, BCF group and JCF group compared with that of the silicosis group. Compared with the same stage of silicosis group, the Ashcroft scores of lung tissues in the YCF group and BCF group were lower in the middle and late stages (all P<0.05). The Ashcroft score of lung tissues in the BCF group in the middle and late stages was lower than that in tetrandrine group at the same stage (all P<0.05), while the Ashcroft score in the middle stages was lower than that in YCF group at the same stage (P<0.05). The Ashcroft score of lung tissue in the JCF group was lower than that in the silicosis group, tetrandrine group and YCF group at all three stages (all P<0.05), and was lower than that in BCF group at the early and late stage of silicosis (all P<0.05). iii) Inflammatory factors. IL-6 level in the lung tissues in the YCF group, BCF group and JCF group decreased compared with that in the silicosis group at the same stage (all P<0.05), while IL-1β and TNF-α levels decreased at the early and middle stages (all P<0.05), hydroxyproline level decreased at all three stages (all P<0.05). iv) Collagen. The relatively expression of COL-Ⅰ in the lung tissues in the YCF group decreased at the late stage of silicosis compared with that in the silicosis group at the same stage (all P<0.05), while the relatively expression of α-SMA decreased at the middle and late stages (all P<0.05). Compared with the same stage of silicosis group, the relative expression of COL-Ⅰ and α-SMA of the lung tissues reduced in the BCF group and JCF group at all stages (all P<0.05). The relative expression of COL-Ⅰ of the lung tissues reduced in the BCF group at the late stage compared with that in the YCF group in the same stage (all P<0.05), while the relative expression of α-SMA decreased at the early and middle stages (all P<0.05). The relative expression of COL-Ⅰ of the lung tissues reduced in the JCF group at late stage of silicosis (all P<0.05), while the relative expression of α-SMA decreased at all three stages (all P<0.05), compared with the same stage of YCF group. Conclusion All three formulations of Chinese herbs are effective in improving lung function and alleviating the progress of lung inflammation and fibrosis. YCF is the most effective in suppressing inflammation in the early stage of silicosis. BCF excels in delaying fibrosis in the early and middle stages. JCF is the most effective in improving lung function and delaying fibrosis progression in the late stage.

Pneumoconiosis is an occupational lung disease with the highest incidence in China. There is no effective treatment drug at present. Animal and cell models are the basis for exploring its pathogenesis and developing effective drugs. In this paper, we sort out the methods of animal models of pneumoconiosis and the different cell models induced by dust in recent years, by analyzing and summarizing the advantages and disadvantages, modeling time, pathology and changes in important indicators of different preparation methods of animal models, as well as different cell models induced by the dust to simulate different pathological models and pathological stages, to provide basis for the application and improvement of pneumoconiosis model.

Pneumoconiosis is an occupational lung disease with the highest incidence in China. There is no effective treatment drug at present. Animal and cell models are the basis for exploring its pathogenesis and developing effective drugs. In this paper, we sort out the methods of animal models of pneumoconiosis and the different cell models induced by dust in recent years, by analyzing and summarizing the advantages and disadvantages, modeling time, pathology and changes in important indicators of different preparation methods of animal models, as well as different cell models induced by the dust to simulate different pathological models and pathological stages, to provide basis for the application and improvement of pneumoconiosis model.

Objective To exploring the mechanism of Jinshui Chenfei formula(JCF)in ameliorating silica(SiO2)-induced silicosis fibrosis based on endogenous metabolite changes.Methods A total of 32 SPF male Sprague-Dawley(SD)rats were divided into normal control group,model group,JCF group(9.72 g·kg-1·d-1),and Tetrandrine group(27 mg·kg-1·d-1)according to random number table method.The experimental silicosis model was established by intratracheal injection with SiO2 suspension(250 mg/kg)on day 1.From week 5-8,silicosis rats were treated with tetrandrine or JCF.On the end of week 8,the changes of pulmonary function index,including forced vital capacity(FVC),tidal volume(TV)and lung dynamic compliance(Cydn)were detected.The pathological changes of lung tissue were analyzed by hematoxyline-osin(HE)staining and Masson staining,the severity of focal alveolitis and fibrosis was also evaluated using the Szapiel scale and the Ashcroft scale,the positive staining of collagen Ⅰ(COL Ⅰ)and COL Ⅲ was detected using immunohistochemistry;the protein expression of transforming growth factor-β1(TGF-β1),fibronectin(FN),andα-smooth muscle actin(α-SMA)were measured by Western blotting.The rat serum samples were further screened for differential metabolites using ultra performance liquid chromatographytandem quadrupole time of flight mass spectrometr(UPLC-Q-TOF-MS)and pathway analysis was performed based on MetaboAnalyst 5.0.Results Compared with those in the normal control group,pathological changes such as alveolar structure destruction,the fibrous nodules encapsulated SiO2 particles were increased in lung tissues of rats in model group,alveolitis score and pulmonary fibrosis score were significantly higher(alveolitis score:2.62±0.27 vs.0.20±0.15,pulmonary fibrosis score:5.42±0.66 vs.0.50±0.84,both P<0.01);pulmonary function index including Cydn,FVC,and TV were significantly decreased[Cdyn(mL/cmH2O):0.26±0.03 vs.0.33±0.03,FVC(mL):8.09±0.47 vs.10.99±0.38,TV(mL):1.95±0.19 vs.2.53±0.26,all P<0.01];positive staining of COL Ⅰ,COL Ⅲ and ɑ-SMA,FN,TGF-β1 proteins expression showed higher in lung tissues[positive staining of COL Ⅰ(A value):13.47±1.76 vs.5.77±0.45;positive staining of COL Ⅲ(A value):10.39±0.47 vs.6.19±0.77,FN protein expression(FN/GAPDH):0.33±0.02 vs.0.21±0.07,α-SMA protein expression(α-SMA/GAPDH):1.78±0.16 vs.1.11±0.24,TGF-β1 protein expression(TGF-β1/GAPDH):0.52±0.10 vs.0.11±0.46,all P<0.01].Compared with the model group,the pathological changes of lung tissues were almost restored,alveolitis score and lung fibrosis score were significantly reduced in JCF and Tetrandrine groups(alveolitis score:1.10±0.15,1.33±0.31 vs.2.62±0.27,pulmonary fibrosis score:3.50±0.45,4.33±0.98 vs.5.42±0.66,all P<0.01);the pulmonary function index Cydn,FVC and TV were significantly increased[Cdyn(mL/cmH2O):0.32±0.05,0.31±0.04 vs.0.26±0.03,FVC(mL):9.41±0.85,8.70±0.92 vs.8.09±0.47,TV(mL):2.70±0.19,2.27±0.15 vs.1.95±0.19,all P<0.05];positive staining of COL Ⅰ,COL Ⅲ,and protein expression of FN,ɑ-SMA,and TGF-β1 in lung tissues was significantly decreased[COL Ⅰ(A value):7.09±0.67,8.13±0.64 vs.13.47±1.76,COL Ⅲ(A value):8.19±0.66,8.52±0.22 vs.10.39±0.47,FN protein expression(FN/GAPDH):0.19±0.06,0.24±0.03 vs.0.33±0.02,α-SMA protein expression(α-SMA/GAPDH):0.89±0.41,0.88±0.08 vs.1.78±0.16,TGF-β1 protein expression(TGF-β1/GAPDH):0.04±0.03,0.06±0.01 vs.0.52±0.10,all P<0.05].Metabolomics analysis showed that a total of 10 major differential metabolites were identified between normal control group,model group and JCF group,including arachidonic acid,palmitic acid,indole-3-acetic acid,propionylcarnitine,(S)-4-hydroxymandelonitrile,nalidixic acid,benzocaine,gramine,4-ethylphenol,N-benzylfor mamide.The differential metabolites in silicosis rats reversed by JCF treatment were mainly enriched,including unsaturated fatty acid biosynthesis,arachidonic acid metabolism,tryptophan metabolism,fatty acid elongation,fatty acid degradation and biosynthesis.Conclusion JCF could effectively improve the silicosis fibrosis,which is mainly related to biosynthesis of unsaturated fatty acids biosynthesis,arachidonic acid metabolism,tryptophan metabolism,fatty acid elongation,fatty acid degradation and biosynthesis.