Abstract:
Objective To explore the intervention effect of calcitriol on silica-induced lung fibrosis in rats and its possible mechanism.
Methods SD rats (n=48) were randomly divided into four groups:control group, model group, solvent group, and calcitriol group, with 12 rats in each group. Rats in the model group, solvent group, and calcitriol group were exposed to 1 mL silica particle suspension (50 mg/mL) intratracheally to establish silicosis rat model, while the control group was exposed to an equal volume of saline using the same protocol. Starting from the day of model establishment, the calcitriol group was given intragastric administration of castor oil-diluted calcitriol (0.5 μg/kg) daily, the solvent group was treated with an equal volume of castor oil, and the control group and the model group were given an equal volume of saline. Six rats of each group were sacrificed randomly at 14 and 28 days after modelling respectively. The pathological changes of lung tissues were observed by HE staining and Masson staining. The content of hydroxyproline was detected by alkaline hydrolysis. The expression of transforming growth factor-β1(TGF-β1), SMA-and MAD-related protein (SMAD) 3, and SMAD7 in lung tissues were detected by immunohistochemistry.
Results The calcitriol group showed alleviative lung inflammation and interstitial fibrosis than the model group. Compared with the model group, the pulmonary organ coefficients and hydroxyproline content were decreased in the calcitriol group (P < 0.05). The protein expressions of TGF-β1 (0.021 9±0.003 1) and SMAD3 (0.036 9±0.001 6) in the calcitriol group were lower than those in the model group(0.036 1±0.002 2) and (0.0420±0.0020) (P < 0.05), and the protein expression of SMAD7 (0.033 3±0.002 1) in the calcitriol group was higher than that of the model group (0.014 4±0.002 4) (P < 0.05). There were no significant differences in above in dicators between the model group and the solvent group (P>0.05).
Conclusion Calcitriol could alleviate silicosis fibrosis in rats, which may be associated with its regulation of protein expression in TGF-β1/SMAD pathway.
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