OBJECTIVE: Recent studies have overturned the traditional concept of the lung as a "sterile organ" revealing that pulmonary microbiota dysbiosis and abnormal surfactant proteins (SPs) expression are involved in the progression of silicosis. This study aimed to investigate the relationship between abnormal SPs expression and dysbiosis of lung microbiota in silica-induced lung fibrosis, providing insights into mechanisms of silicosis. METHODS: Lung pathology, SPs expression, and microbiota composition were evaluated in silica-exposed mice. A mouse model of antibiotic-induced microbiota depletion was established, and alveolar structure and SPs expression were assessed. The roles of the lung microbiota and SPs in silicosis progression were further evaluated in mice with antibiotic-induced microbiota depletion, both with and without silica exposure. RESULTS: Silica exposure induced lung inflammation and fibrosis, along with increased expression of SP-A expression. Antibiotics (Abx)-induced microbiota depletion elevated SP-A and SP-D expression. Furthermore, silica exposure altered lung microbiota composition, enriching potentially pathogenic taxa. However, antibiotic-induced microbiota depletion prior to silica exposure reduced silica-mediated lung fibrosis and inflammation. CONCLUSION Lung microbiota is associated with silica-induced lung injury. Overproduction of SP-A and SP-D, induced by Abx-induced microbiota depletion, may enhance the resistance of mouse lung tissue to silica-induced injury.
Animals ; Silicosis/prevention & control* ; Lung/metabolism* ; Mice ; Anti-Bacterial Agents/pharmacology* ; Microbiota/drug effects* ; Silicon Dioxide/toxicity* ; Mice, Inbred C57BL ; Male ; Pulmonary Surfactant-Associated Proteins/genetics*

Humans ; Nutrition Assessment ; Prognosis ; Silicosis/prevention & control* ; Occupational Diseases ; China/epidemiology* ; Occupational Exposure ; Silicon Dioxide

OBJECTIVE: Silicosis, caused by inhalation of silica dust, is the most serious occupational disease in China and the aim of present study was to explore the protective effect of Ang (1-7) on silicotic fibrosis and myofibroblast differentiation induced by Ang II. METHODS: HOPE-MED 8050 exposure control apparatus was used to establish the rat silicosis model. Pathological changes and collagen deposition of the lung tissue were examined by H.E. and VG staining, respectively. The localizations of ACE2 and α-smooth muscle actin (α-SMA) in the lung were detected by immunohistochemistry. Expression levels of collagen type I, α-SMA, ACE2, and Mas in the lung tissue and fibroblasts were examined by western blot. Levels of ACE2, Ang (1-7), and Ang II in serum were determined by ELISA. Co-localization of ACE2 and α-SMA in fibroblasts was detected by immunofluorescence. RESULTS: Ang (1-7) induced pathological changes and enhanced collagen deposition in vivo. Ang (1-7) decreased the expressions of collagen type I and α-SMA and increased the expressions of ACE2 and Mas in the silicotic rat lung tissue and fibroblasts stimulated by Ang II. Ang (1-7) increased the levels of ACE2 and Ang (1-7) and decreased the level of Ang II in silicotic rat serum. A779 enhanced the protective effect of Ang (1-7) in fibroblasts stimulated by Ang II. CONCLUSION Ang (1-7) exerted protective effect on silicotic fibrosis and myofibroblast differentiation induced by Ang II by regulating ACE2-Ang (1-7)-Mas axis.
Actins ; metabolism ; Angiotensin I ; blood ; pharmacology ; therapeutic use ; Angiotensin II ; blood ; Animals ; Animals, Newborn ; Cell Differentiation ; drug effects ; Cells, Cultured ; Collagen Type I ; metabolism ; Disease Models, Animal ; Lung ; metabolism ; pathology ; Myofibroblasts ; drug effects ; Peptide Fragments ; blood ; pharmacology ; therapeutic use ; Peptidyl-Dipeptidase A ; metabolism ; Rats, Wistar ; Silicosis ; metabolism ; pathology ; prevention & control

OBJECTIVETo study the current situation of the prevention and treatment of silicosis in Jinshan District of Shanghai, China, and to provide a scientific basis for the introduction of preventive and control measures for the disease.

METHODSAn occupational hygienic investigation was carried out among enterprises exposed to silica dust hazard in Jinshan District using cross-sectional epidemiological study. Based on GBZ 159-2004 Specifications of air sampling for hazardous substances monitoring in the workplace and GBZ/T 192.1-2007 Method for determination of dust in the air of workplace Part 1: Total dust concentration, individual sampling and evaluation of test results were conducted among workers exposed to silica dust.

RESULTSA total of 302 workers in 30 enterprises were exposed to silica dust, and the coverage of employment injury insurance and occupational health inspection rate were 98.3% and 92.4%, respectively. The equipment rate of anti-dust respirators of the enterprises was 56.7%, and the qualification rate of silica dust monitoring in work place was 40.4%. The enterprises exposed to silica dust were mainly those who were operated in dry condition and engaged in manual work using opening-type equipment without negative pressure.

CONCLUSIONEnterprises exposed to silica dust in Jinshan District of Shanghai have safety hazards like poor production and protective equipment, incomplete protective articles, and low qualification rate of silica dust test in workplace, so occupational health protection measures need to be strengthened.

Air Pollutants, Occupational ; analysis ; China ; Cross-Sectional Studies ; Dust ; analysis ; Humans ; Occupational Exposure ; prevention & control ; Occupational Health ; standards ; Silicosis ; prevention & control ; therapy ; Workplace

OBJECTIVETo investigate the inhibitory effects of CD36-targeting RNA interference on the latent transforming growth factor β1 (L-TGF-β1) activation and silicotic fibrosis in rat silicosis model.

METHODSWistar rats were divided into four groups: saline control group (n=24), SiO2 model group (10 mg SiO2 per rat) (n=24), SiO2+Lv-shCD36 group (lentiviral vector expressing specific shRNA against CD36) (n=24), and SiO2+Lv-shCD36-NC group (non-silence control lentivirus) (n=24). At 7, 21, and 28 d after instillation, the rats were sacrificed. The activity of TGF-β1 in bronchoalveolar lavage fluid (BALF) was measured by evaluating its inhibitory effect on the proliferation of mink lung epithelial cells. The pathological changes of lung tissue were observed by HE staining and van Gieson staining. The hydroxyproline content in the lungs was determined by alkaline lysis method.

RESULTSAt 7 d after instillation, the expression of CD36 mRNA in alveolar macrophages was significantly lower in the SiO2+Lv-shCD36 group than in the saline control group, SiO2 model group, and SiO2+Lv-shCD36-NC group (P < 0.05); the quantity and percentage of active TGF-β1 in BALF were significantly lower in the SiO2+Lv-shCD36 group than in the SiO2 model group and SiO2+Lv-shCD36-NC group (P < 0.05). At 28 d after instillation, there were cellular silicotic nodules in the lungs of rats in SiO2+Lv-shCD36 group and fibrotic cellular silicotic nodules in the lungs of rats in SiO2 model group and SiO2+Lv-shCD36-NC group. At 21 and 28 d after instillation, the hydroxyproline content was significantly lower in the SiO2+Lv-shCD36 group than in the SiO2 model group and SiO2+Lv-sh CD36-NC group (P < 0.05).

CONCLUSIONCD36-targeting RNA interference has inhibitory effects on the L-TGF-β1 activation and silicotic fibrosis in rat silicosis model.

Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; CD36 Antigens ; genetics ; metabolism ; Disease Models, Animal ; Female ; Hydroxyproline ; chemistry ; Macrophages, Alveolar ; metabolism ; Male ; RNA Interference ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity ; Silicosis ; metabolism ; prevention & control ; Transforming Growth Factor beta1 ; metabolism

Humans ; Silicosis ; prevention & control

OBJECTIVETo compare the difference of effects on SiO(2)-induced alveolitis and early fibrosis between bone marrow-derived mesenchymal-like stem cells (BM-MSCs) and BM-MSCs transfected by pcDNA3.1-HGF and to explore the mechanism of this effects.

METHODSThe Primary BM-MSCs from Wistar male young rats were cultured and labeled by 4, 6-diamidino-2-phenylindole (DAPI). Fifty Wistar rats were randomly divided into 3 groups:model group (10 rats),which was administered with SiO(2) by the trache, the next day,injected PBS via the tail vein; BM-MSCs group (20 rats),which was administered with SiO(2) by the trache, the next day,injected with 1 ml suspension of BM-MSCs via the tail vein; pcDNA3.1-HGF plus BM-MSC group (20 rats),which was administered with SiO(2) by the trache, the next day,injected with 1 ml suspension of BM-MSCs transfected by pcDNA3.1-HGF via the tail vein. On the 14th and 28th days after treatment, half of the animals were sacrificed, respectively, and the lungs were harvested for frozen section to observe the cell marked by DAPI. HE staining under a fluorescent microscope, and to observe the pulmonary alveolitis and fibrosis by HE and Masson staining under a light microscope. Western blot assay was used to detect the expression of HGF in rat lungs. The expression levels of tumor necrosis factor-α (TNF-α) in pulmonary tissues were analyzed quantitatively by ELISA. The contents of HYP in pulmonary tissues were analyzed quantitatively by sample hydrolysis method.

RESULTSOn the 14th and 28th days after treatment, the scores of pulmonary alveolitis and early fibrosis in pcDNA3.1-HGF plus BM-MSCs group were 2.36 ± 0.17, 2.8 ± 0.14 and 0.1 ± 0.11, 1.16 ± 0.13, which were significantly lower than those (1.68 ± 0.17, 1.58 ± 0.31 and 0.54 ± 0.15, 1.36 ± 0.13) in BM-MSCs group, also which were significantly lower those (2.36 ± 0.17, 2.80 ± 0.14 and 0.64 ± 0.09, 1.84 ± 0.17) in model group (P < 0.05); On the 14th and 28th days after treatment, the TNF-α contents of pulmonary tissues in pcDNA3.1-HGF plus BM-MSCs group were 280.4 ± 23.11 and 249.78 ± 22.33 pg/mg, which were significantly lower than those (341.58 ± 35.34, 442.29 ± 36.76 pg/mg and 319.51 ± 17.84, 348.53 ± 33.95 pg/mg) in BM-MSCs and model groups (P < 0.05); On the 14th and 28th days after treatment, the HYP contents of pulmonary tissues in pcDNA3.1-HGF plus BM-MSCs group were 0.46 ± 0.04 and 0.65 ± 0.05 µg/mg, which were significantly lower than those (0.63 ± 0.04, 1.04 ± 0.07 µg/mg and 0.72 ± 0.60, 1.39 ± 0.60 µg/mg) in BM-MSCs and model groups (P < 0.05).

CONCLUSIONThe effects of BM-MSCs transfected by pcDNA3.1-HGF on suppressing pulmonary alveolitis and early fibrosis induced by SiO2 were better than those of BM-MSCs. The mechanism may be associated with the reduced pulmonary inflammation.

Animals ; Bone Marrow Cells ; cytology ; Hepatocyte Growth Factor ; genetics ; metabolism ; Male ; Mesenchymal Stromal Cells ; metabolism ; Pulmonary Fibrosis ; chemically induced ; prevention & control ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity ; Silicosis ; prevention & control ; Transfection

OBJECTIVETo investigate the effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on the collagen synthesis and expression in lung of rats with silicosis.

METHODSRats were divided into 6 groups randomly, 10 rats in each group: Control 1 of silicotic model: each rat was intratracheally instilled with 1 ml normal sodium and was killed at the fourth week; Control 2 of silicotic model: each rat was intratracheally instilled with 1 ml normal sodium and was killed at the eighth week; Silicotic model 1: each rat was intratracheally instilled with 1 ml silica suspension and was killed at the fourth week; Silicotic model 2: each rat was intratracheally instilled with 1 ml silica suspension and was killed at the eighth week; Anti-fibrosis treatment of AcSDKP: after each rat was intratracheally instilled with 1 ml silica suspension for 4 weeks, AcSDKP 800 microg/(kgxd) was administered into every rat and rats were killed at the eighth week; Preventing fibrosis treatment of AcSDKP: after AcSDKP 800 microg/(kgxd) was administered into every rat for 48 hours, each rat was intratracheally instilled with 1 ml silica suspension and rats were killed at the eighth week. Lung fibrosis in morphology was observed by HE and VG staining. Collagen content was detected by hydroxyproline assay. The expression of type I and III collagen was evaluated by western blot.

RESULTSCompared with those of silicotic model 1 and silicotic model 2 group, in anti-fibrosis treatment of AcSDKP group, the area of silicosis nodules decreased to 84.28% and 67.93%, the content of hydroxyproline decreased to 70.89% and 58.18%, the expression of type I collagen decreased to 71.08% and 58.13%, and expression of type III collagen decreased to 80.13% and 70.70%. Compared with those of silicotic model 2 group, in preventing fibrosis treatment of AcSDKP group, area of silicosis nodules decreased to 61.13%, content of hydroxyproline decreased to 60.27%, and expression of type I and type III collagen decreased to 40.13% and 65.77%.

CONCLUSIONAcSDKP could obviously inhibit the synthesis and expression of collagen in lung of rats with silicosis, which is possibly related with anti-fibrosis effect of AcSDKP.

Animals ; Collagen ; metabolism ; Disease Models, Animal ; Drug Antagonism ; Lung ; drug effects ; metabolism ; pathology ; Male ; Oligopeptides ; pharmacology ; Pulmonary Fibrosis ; pathology ; prevention & control ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity ; Silicosis ; metabolism ; pathology

Anthracosis ; prevention & control ; Humans ; Silicosis ; prevention & control ; South Africa

OBJECTIVETo investigate the anti-fibrotic effects of Qidan granule in rats.

METHODSThe rats were randomly divided into six experimental groups: normal group, model group, Qidan group, Tetrandrine group. All rats except normal group were treated with silicon dioxide (50 mg/rat) by intratracheal instillation to induce silicosis. Qidan group and Tetrandrine group were treated with Qidan granule (3125 mg/kg) or treated with Tetrandrine (22 mg/kg) respectively. All the rats were sacrificed after 5 months. Calculate Lung/body coefficient by weighting the lung wet weight and the body weight of rats. Content of Hydroxyproline was measured by alkaline hydrolysis. The gene expression of transforming growth factor-beta1 was examined by using enzyme-linked immunosorbent assay (ELISA). Paraffin embedded lung sections with HE staining, VG staining and Gomori staining were observed under light microscope.

RESULTSIn Qidan group and Tetrandrine group, Lung/body coefficient and content of Hydroxyproline and expression of transforming growth factor-beta1 were lower as compared with model group (P < 0.05). Model group mainly showed III approximately IV grade silicotic nodule, which contained thick collagen and sparse reticulum fibe; Qidan group and Tetrandrine group appeared with II grade silicotic nodule, which contained tiny collagen and intensive reticulum fibe. Tetrandrine group showed injury of kidney, and others were normal.

CONCLUSIONQidan granule extract should prevent and from inhibit the remarkably silicotic fibrosis in rats.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Phytotherapy ; Pulmonary Fibrosis ; pathology ; prevention & control ; Rats ; Rats, Wistar ; Silicosis ; drug therapy ; metabolism ; pathology ; Transforming Growth Factor beta ; biosynthesis