[Up-regulation of molecules associated with Sonic hedgehog signaling pathway plays a protective role in mouse acute lung injury induced by lipopolysaccharide].

OBJECTIVE: To explore the expression changes and significance of Sonic hedgehog (SHH) signaling pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI). METHODS: The experimental animals were randomly divided into control group, LPS-treated group (LPS 5 mg/kg) and cyclopamine-treated group (cyclopamine 50 mg/kg). The pathological changes of lung tissues were observed with HE staining, and the lung wet to dry mass ratio (W/D) was measured. Real-time quantitative PCR (RT-PCR) was used to detect the mRNA expressions of tumor necrosis factor α (TNF-α), SHH, Patched (PTC) and downstream transcription factor GLI1 in lung tissues, and Western blotting was adopted to determine the protein levels of SHH and GLI1 in lung tissues. RESULTS: Pathological injury score of lung tissues, W/D and mRNA level of TNF-α were significantly higher in the LPS-treated group than in the control group. Compared with the control group, the mRNA levels of SHH, PTC and GLI1 in the LPS-treated group were not significantly different at 6 hours and were remarkably higher at 12 and 24 hours, with a positive correlation with the time. Protein expression levels of SHH and GLI1 at 6, 12 and 24 hours in the LPS-treated group showed a more notable increase than those in the control group, and a positive correlation with the time was displayed. After cyclopamine intervention, the mRNA levels of SHH, PTC and GLI1 and the protein levels of SHH and GLI1 were all reduced, while pathological injury score of lung tissues, W/D and mRNA level of TNF-α were obviously higher than those in the LPS-treated group. CONCLUSION: SHH signaling pathway was activated in the development process of LPS-induced ALI, and up-regulated expressions of SHH signaling pathway associated molecules could relieve lung injury and involve repair of the injured lung tissues.