ex-527 and Shock--Septic

This study was designed to investigate the effects and the mechanism of Tanshinone IIA (TIIA) on endotoxic shock-induced lung injury in a mouse model.. Mice were administered intraperitoneally with TIIA (10 mg/kg) 0.5 h before lipopolysaccharide (LPS) challenge and then received additional injections every 24 h during the 3-day experimental period. The physiological indexes, the survival rate and the parameters for lung injury were examined. The protein levels of Sirt1, and the acetylation and activation of NF-κB p65 were determined. The expression and secretion of pro-inflammatory factors were evaluated, respectively.. Treatment with TIIA significantly improved physiological indexes and increased the survival rate of mice in response to LPS challenge. TIIA treatment displayed an obvious up-regulation of Sirt1 protein, in accompany with reduced acetylation and activation of NF-κB p65 following LPS stimulation. In addition, TIIA attenuated LPS-induced lung injury and prevented the expression and secretion of pro-inflammatory factors. However, the protective effects of TIIA were abolished by Sirt1 inhibitor.. Tanshinone IIA prevents LPS-induced secretion of pro-inflammatory cytokines thus exerts protective effects against acute lung injury, probably via modulation of Sirt1/NF-κB signalling pathway.

Topics: Abietanes; Acute Lung Injury; Animals; Carbazoles; Cytokines; Lipopolysaccharides; Lung; Mice; Mice, Inbred C57BL; Shock, Septic; Signal Transduction; Sirtuin 1; Transcription Factor RelA