| Summary: | 碩士 === 國防醫學院 === 生理學研究所 === 101 === The characterization of acute lung injury (ALI) includes the impairment of the alveolar-capillary barrier, with the accumulation of protein rich fluid and influx of inflammatory cells into the alveolar airspace, all of which are associated with pulmonary cells damage. 7,8-Dihydroxyflavone (7,8DHF), a Tyrosine kinase receptor B agonist, exerts an anti-apoptosis effect against tissue injury in endotoxemia rats. However, whether 7,8DHF has a beneficial effect on lipopolysaccharide (LPS)-induced ALI is unreported. The aim of this study was to investigate the effects of the 7,8DHF on LPS-induced lung injury, and further elucidated the mechanism involved. Intratracheally injection of LPS (5 mg/kg) in Rats after 3 hours we given intraperitioneal injections of 7,8DHF (20 ,50 mg/kg). After 3 hours, 7,8DHF significantly attenuated the symptoms of ALI, reflected by attenuation of Wet/dry ratio of the lungs, protein concentration and number of total WBC counts in bronchoalveolar lavage fluid (BALF) accompanied with the lung pathological changes. Meanwhile, 7,8DHF significantly decreased myeloperoxidase activity and the levels of superoxide and nitrite/nimate in lung tissue, and alleviated LPS-induced the production of TNF-α, IL-6, IL-1β, MIP-2 in BALF. Furthermore, 7,8DHF increased phosphorylation level of TrkB in ALI . In addition, 7,8DHF significantly diminished ROS formation and inhibited caspase-3 gene expression in lung tissue, accompanied by reduced apoptosis. In conclusion, we demonstrate for the first time that treatment with 7,8DHF exerts a beneficial effect in LPS-induced lung injury through decrease of proinflammatory mediators formation, but enhancement of TrkB expression, subsequently leading to attenuation of apoptosis. In conclusion, we demonstrate that 7,8DHF exerts a beneficial effect in LPS-induced lung injury, which may be associated with increase of TrkB activation and decrease apoptosis
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