Background Silicosis is the most serious occupational disease, and there is no specific treatment plan. It had been found that coenzyme Q10 (CoQ10) can relieve methotrexate-induced pulmonary fibrosis, but whether it can alleviate silicosis fibrosis has not been reported; in addition, it has not been reported whether hydroxymethyl glutaryl coenzyme A reductase (HMGCR), as a rate limiting enzyme for endogenous synthesis of CoQ10, has changed in this process.
Objective This experiment investigates the effect of CoQ10 on silicosis fibrosis in mice and the associated potential change of HMGCR.
Methods C57BL/6 mice were randomly divided into three groups:control group (saline group), model group (SiO2 group), and treatment group (SiO2+CoQ10 group), with eight mice in each group. Every mouse in the model group and the treatment group was exposed to 0.1 mL SiO2 suspension (50 mg/mL) by intratracheal instillation to build mouse silicosis model, while the control group was instilled with the same volume of normal saline. After 48 h of model establishment, the mice in the treatment group were given 100 mg/(kg·d) CoQ10 by gavage. After 60 d, all mice were sacrificed. The pathological changes and collagen deposition were observed after HE and Sirius red staining. The hydroxyproline (HYP) content in the lung tissues of mice was detected by alkaline hydrolysis. The alpha smooth muscle actin (α-SMA) mRNA expression was detected by real-time quantitative fluorescence PCR. The α-SMA and HMGCR protein expressions were detected by immunohistochemistry and Western blot.
Results Inflammatory cell infiltration and fibrosis were more prominent in the model group than in the control group, and less severe in the treatment group than in the model group. The HYP content of the model group was (0.65±0.06) μg/mg, which was higher than that of the control group(0.54±0.05) μg/mg, while the HYP content of the treatment group was (0.55±0.05) μg/mg, which was lower than that of the model group (P < 0.05). The relative expression levels of α-SMA mRNA in the control group, the model group, and the treatment group were 24 381.85±3 301.44, 31 812.66±8 335.82, and 21 587.55±9 489.53, respectively; the expression of α-SMA mRNA in the model group was higher than those in the control group and the treatment group (P < 0.05). The expression levels of α-SMA and HMGCR proteins were higher in the model group than in the control group, and lower in the treatment group than in the model group (P < 0.05).
Conclusion CoQ10 can attenuate silicosis fibrosis and reduce HMGCR expression in mice.
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