[The relationship between HIF-1α expression and the early lung fibrosis in rats with acute paraquat poisoning]

To explore the role of hypoxia-inducible factor 1alpha (HIF-1α) in early lung fibrosis of rats with acute paraquat (PQ) poisoning.

Forty eight healthy SD rats were randomly divided into control group (6 rats) and paraquat poisoning group (42 rats). Control group was exposed to 1 ml normal solution by gastric gavage. The paraquat group was exposed to 1 ml paraquat solution (50 mg/kg) by gastric gavage for 2, 6, 12, 48, 72 and 120 h, respectively. The arterial blood gas analysis (PaO(2)) was detected. The pathological examinations of lung tissues were performed by HE and Mason staining. HIF-1α in lung tissues were measured by immunofluorescence. Western blot assay was used to detect the expression levels of HIF-1α protein in lung tissues.

PaO2 of rats exposed to paraquat for 72 h was (62.33 ± 0.22) mm Hg, which was significantly lower than that (96.00 ± 5.20) of control group (P < 0.05). Pathological examination by HE staining indicated that the acute diffuse lesion appeared in the alveolar capillary endothelium, epithelia and interstitial tissues, and there was the inflammatory cell infiltration in the alveolar of rats exposed to paraquat at 2 h after exposure. At 12 h after exposure, the interstitial edema in lung tissues of rats decreased and the alveolar space became narrow. At 120 h after exposure, there were the alveolar structure derangement, abundant cicatrix, more fibroblasts and peripheral inflammation absorption. Pathological examination by Masson staining showed that there was obvious collagen deposition in the alveolar epithelia at 2h after exposure, the increased collagen fibrosis at 24 and 48 h after exposure and the obvious damage of alveolar tissues or much more fibrous connective tissue deposition at 120 h after exposure. The results of western blot and immunofluorescence assays exhibited that the expression levels of HIF-1α in lung tissues at 2, 24 and 48 h after exposure significantly increased, as compared with control group (P < 0.05), but there were no significant differences of HIF-1α expression among sub-groups at different time points after exposure.

The results of present study shown that there were the pulmonary fibrosis and increased expression of HIF-1α in acute PQ poisoning rats at the early stage, and HIF-1α may be associated with pulmonary fibrosis.