The Mechanism Of LPS-induced Acute Lung Injury In Mice And The Protect Mechanism Of MgSO₄ On Acute Lung Injury

Background:The mortality rate of acute lung injury (ALI) as high as 40%-70%, ALI poses a great threat to human health. The cause of ALI varied, so its pathogenesis are complex. At present, the study about pathogenesis of ALI is not enough systematic and comprehensive. Clinically, there is no very effective treatments. Lipopolysaccharide (LPS) is a component of the cell wall of Gram-negative bacteria, is the main cause of ALI. Studies have shown that, MgSO4 has certain anti-inflammatory effects, can inhibit oxidative stress, is likely to be a better protective agent, but its protective mechanisms in ALI induction by LPS has not been reported.Objectives:To investigate the mechanism of LPS-induced ALI in mice, study the protective mechanism of MgSO4 in LPS-induced ALI. Revealing the pathogenesis of LPS-induced ALI, and to find effective clinical treatments.Methods:Models of ALI was prepared in mice via injection LPS, the evaluated of the model was using histopathology and ELISA.The analysis of oxygen free radicals and necrosis protein in LPS-induced ALI in mice were use the flow cytometry and Western blot, to explore the mechanism of LPS-induced ALI in mice and the protect of MgSO4 in ALI.Results:(1) After injection LPS, mice lung tissue edema, alveolar permeability increases; alveolar damage, a lot of neutrophil accumulation, inflammatory cell infiltration, tissue damage;.The content of TNF-α, IL-6, IL-8, IL-1β and ICAM-1 in BALF and serum was significantly higher than the control group.(2) After mice and A549 cells infected by LPS, ROS, NO and MDA were significantly higher than the control group in tissues and cells, the expression of necrosis protein PARP-1 and its downstream protein AIF was significantly upregulated; after the antioxidants NAC and LPS treatment A549 cells together, found that the rate of cell death was significantly reduced compared with LPS, the levels of necrosis protein PARP-1 and its downstream protein AIF was significantly reduced compared with LPS group.(3) MgSO4 can ease the mice lung injury induced by LPS and reduce the expression of TNF-q and IL-1β. MgSO4 down regulation the expression of necrosis protein PARP-1 and its downstream protein AIF, reduced cell necrosis rate.Conclusion:(1) LPS-induced ALI can produce too much oxygen free radicals, cause oxidative stress in mice, increased the expression of necrosis protein PARP-1 and its downstream protein AIF, then participating in the development and progression of acute lung injury.(2) MgSO4 has a protective effect on LPS-induced ALI in mice, and it may across inhibiting the expression of necrosis proteins PARP-1 and its downstream protein AIF, thus reducing the rate of cell necrosis, and play a protective role at ultimately.