The presem study was designed to find ota whether SB432542, an inhibitor of transfomung growth factor B1activin receptor-like kinase, could protect the lung from LPS-induced injury. Inflanxatory lung injury model was inducedby inUatracheal administration of LPS. C57BL/6 mice were randomly divided imo the sham control group (S group), theLPS stimulation group (L group), the LPS+early S8431542 treatment group (1e group), and the LPS+delayed SB432542treabnent group (Id group). S8431542 was admitted intraperitoneally on study days 1, 2, and 3 to the mice in 1e group,whereas those in Id group received the same dose of SB432542 on days 4, 5, and 6. Pulmonary TNF-u and IL-1p mRNA expressions were tested. Pathological evaluaLOns of pulmonary alveolnis and collagen deposition and fibrosiswere performed on study days 7 and 28, along with the determination of pulmonary hydroxyproline, matrixmetalbproteinase 9, and tissue inhibitor of matrix metalloproleinase 1 on study day 2E. As a result, LPS stimulationresulted in significant increases of the pulmonay TNF-a and IL-16 mRNA expressions as web as pathological scores foralveolitis on day 7 and increased collagen deposition, hydroxyproline content, and pathological scores for fibrosis on day即。with a decrease of malnx metalloproteinase S activity. Those parameters were further aggravated in the 1e groupvahereas relieved significantly in the Id group. These data suggest that SB43t542 therapy for inflammatory lung ir,lurycould be harmful if performed Miring early-phase inflatntnatory response. However, the ttterapy would prevent lung frominflanmatory injury and fibrosis i1 it was initiated late.
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