Abstract:
Background The pathological changes of silicosis are mainly the formation of massive fibrosis and sputum nodules. Some patients with silicosis show severely impaired lung function. Currently, there is no effective clinical therapy for the disease. Histone deacetylase inhibitors are involved in many diseases, but their role in pulmonary fibrosis in mice is not known.
Objective This experiment is designed to explore the effect of histone deacetylase inhibitor, panobinostat, on the silicosis fibrosis in silica-treated mice.
Methods Twenty-eight C57BL/6 male mice were randomly divided into four groups:control group, model group, panobinostat treatment group, and panobinostat drug control group. The model group was intranasally instilled with 100 mg/mL SiO2 suspension at 50 μL for seven consecutive days; the panobinostat treatment group was additionally given intraperitoneal injection of panobinostat at 5 mg/kg per day, three times per week, from day 8 for three consecutive weeks; the panobinostat drug control group was given only the drug; and the control group was given normal saline. The lung function of the mice was detected on day 48, and then the mice were sacrificed. The content of hydroxyproline in the lung tissues was detected by corresponding kit. The pathological changes of lung tissue samples were observed with HE staining. The expressions of type Ⅰ collagen and type Ⅲ collagen in mouse lung tissue samples were observed with sirius red staining. The secretion of transforming growth factor β1 (TGF-β1) in serum and bronchoalveolar lavage fluid (BALF) of the mice were determined by ELISA.
Results Compared with the control group, the model group showed obviously increased infiltration of inflammatory cells, silicotic nodules, and type Ⅰ and type Ⅲ collagens; increased hydroxyproline content(1 008.43±182.07) mg/g versus the control group(566.83±120.22) mg/g; increased contents of TGF-β1 in BALF and serum(109.97±2.14) and (934.65±68.13)mg/L versus the control group(52.62±3.57) and (540.36±1.06)mg/L, which were all statistically significant (P < 0.05). Compared with the model group, the panobinostat treatment group showed effectively reduced silicotic nodules, hydroxyproline(824.08±94.88) mg/g, and type Ⅰ and type Ⅲ collagens. Furthermore, panobinostat significantly improved the lung function of mice as the respiratory rate and of airway stenosis coefficient were (318.14±9.77) breaths/min and (2.22±0.41) in the model group, and (378.95±36.47) breaths/min and (1.59±0.12) in the panobinostat treatment group; panobinostat also down-regulated TGF-β1 in BALF and serum(72.15±8.81) and (765.46±86.99)mg/L respectively.
Conclusion Panobinostat can obviously alleviate silicosis fibrosis and improve the lung function of silicotic mice.
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