Expression of discoidin domain receptor 1 in the rat with pulmonary fibrosis induced by acute paraquat ;poisoning / 中华危重病急救医学

ABSTRACT

Objective To explore the expression of discoidin domain receptor 1 (DDR1) in rats with pulmonary fibrosis induced by paraquat (PQ) poisoning, and its relationship with the expression of transforming growth factor-β1 (TGF-β1). Methods 120 Sprague-Dawley (SD) rats were divided into control group and 20, 40, and 80 mg/kg PQ poisoning groups (each n = 30). Pulmonary fibrosis induced by PQ poisoning model was reproduced by one time administration of 20, 40, 80 mg/kg of 20% PQ, and the rats in control group were given 4 mL normal saline. Fifteen rats in control and different doses of PQ groups were sacrificed at 7 days and 21 days after intragastric administration, and lung tissues were collected. Pulmonary fibrosis was observed after hematoxylin-eosin (HE) staining. The immune-histochemical method was used to determine the expressions of DDR1 and TGF-β1. The relationship between the expression of TGF-β1 and DDR1 was analyzed by Pearson correlation analysis. Results The rats in control group were active, and no pathological changes in lung tissue were found. The rats in PQ groups became shortness of breath, bristles, and slow reaction etc. 0.5 hours after intragastric administration. After 7 days, the lung tissue was dark red, hard texture, appearance of yellow soil fiber nodules and obsolete hemorrhage, destruction of alveolar structure. The extent of lung injury increased gradually with the time of poisoning and the increase of PQ dose. It was shown by immune-histochemical staining that the control group had only a small amount of DDR1 and TGF-β1 positive expressions; in PQ groups, there were a large number of DDR1 and TGF-β1 positive expression particles in the alveolar wall, pulmonary interstitial and alveolar cavity. It was displayed by quantitative analysis that compared with the control group, DDR1 and TGF-β1 expressions were significantly increased in 20, 40, 80 mg/kg PQ groups with time- and dose-dependent [DDR1 (integral A value) 0.221±0.014, 0.249±0.021, 0.364±0.016 vs. 0.121±0.036 at 7 days; 0.247±0.025, 0.321±0.015, 0.432±0.027 vs. 0.139±0.021 at 21 days; TGF-β1 (integral A value) 0.230±0.016, 0.265±0.015, 0.339±0.016 vs. 0.129±0.032 at 7 days; 0.248±0.011, 0.295±0.016, 0.399±0.026 vs. 0.119±0.026 at 21 days; all P < 0.05]. It was shown by Pearson correlation analysis that DDR1 expression was positively correlated with TGF-β1 expression with the increase of PQ dose and poisoning time (DDR1 with TGF-β1 r = 0.996, P < 0.000; DDR1 with PQ dose r = 0.985, P < 0.000; DDR1 with poisoning time r = 0.989, P < 0.000; TGF-β1 with PQ dose r = 0.992, P < 0.000; TGF-β1 with poisoning time r = 0.972, P < 0.000). Conclusions The expression of DDR1 in the lung tissue in PQ poisoning rats showed a time- and dose-dependent change, and it was positively correlated with TGF-β1 expression. DDR1 may be involved in the process of pulmonary fibrosis induced by PQ poisoning.