Effects And Mechanism Of Simvastatin On LPS-induced A-ENaC MRNA In Lung Alveolar Type â…¡ Epithelial Cells

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are common respiratory complications in clinic, especially in intensive care unit (ICU), and important changes in physiology arid pathology will result from evident increase of the amount of lung water, in traditional ideas, the passive process that the reabsorption of lung water relying on hydrostatic pressure can be explanted by Starling equation, but it doesn't work in recent researches that active water and sodium transport system of alveolar epithelial cells play a part in the reabsorption of lung fluid。Recent researches find that simvastatin can be used not only in fat decrease, but also in Anti-inflammation, immunity modulation, protection of endothelial cells, and alleviation of dysfunction of coagulation。Aims:Objective to set up an acute-detached AT-Ⅱmodel of rats for LPS induced external cultivation.1st observation, the impact from simvastatin on LPS induced alveolar epithelial cells,2nd, the impact from simvastatin on the secretion of TNF-α, IL-1β.To explore the impact from simvastatin on LPS induced alveolar epithelial cells, to infere whether simvastatin can be helpful in removing lung fluid and the possible mechanism, based on this, to provide new way to cure Pulmonary Edema. Methods:all AT-Ⅱof rats were detached and purified, and put into tissue culture flasks,2x106 in each flask, then separate flasks into 5 groups, groupⅠ:only containing DMEM culture medium substrate, groupⅡ: group LPS, containing LPS (final concentration 1μg/ml)+DMEM culture medium substrate, groupⅢ:simvastatin group 1, DMEM culture medium substrate+LPS (final concentration 1μg/ml)+simvastatin (final concentration 20μmol/l), groupⅣ:simvastatin group 2, DMEM culture medium substrate+LPS (final concentration 1μg/ml)+simvastatin (final concentration 30μmol/l), groupⅤ:solution control group, DMEM culture medium substrate+0.1mol/1 NaOH+40% ethanol+HC1. LPS was added into groupⅢandⅣafter simvastatin was added half an hour later. groupⅢandⅣco-cultured for 1 hour,12 hours,24 hours, and then ENaC-mRNA, TNF-α, and IL-1βwere tested for 5 times, record the results.Results:(1) After being intervened for 1 hour, the expressions of TNF-αand IL-βboth increased (P<0.05) in LPS injured group (groupⅡ) Compared with those in blank group (groupⅠ),while no evident increase in expression ofα-ENaCmRNA was observed。Expressions of TNF-αand IL-βin Simvastatin intervened group (groupⅢ-Ⅳ) both increased (P<0.05) compared with blank group, but decrease (P<0.05) while compared with LPS injured group, and no evident changes observed in the expression ofα-ENaCmRNA in groupⅢandⅣ。Expressions of TNF-αand IL-1βin groupⅣ(30μmol/L S imvastatin) was lower than that of groupⅣ(20μmol/L S imvastatin). No evident difference (P>0.05) in the expression ofα-ENaCmRNA, TNF-α, and IL-βin Solution group (groupⅤ) compared with blank group (groupⅠ)。2)After being intervened for 12 and 24 hours, the expressions of TNF-αand IL-βboth evidently increased (P<0.05), evident decrease in expression of a-ENaCmRNA was observed (P<0.05) in LPS injured group (groupⅡ) Compared with those in blank group (groupⅠ)。Expressions of TNF-α, IL-βin simvastatin intervened group (groupⅢ-Ⅳ) increased (P<0.05) compared with blank group, but decreased (P<0.05) while compared with LPS injured group (groupⅡ),expressions of a-ENaCmRNA in simvastatin intervened group (groupⅢ-Ⅳ) decreased (P<0.05) compared with blank group, but increased (P<0.05) while compared with LPS injured group (groupⅡ)。The expressions of TNF-αand IL-βin groupⅢ(20μmol/L simvastatin) increased than that of groupⅣ(30μmol/L simvastatin)。Expression of a-ENaCmRNA decreased (P<0.05) (groupⅢcompared with groupⅣ)。while No evident difference in expressions ofα-ENaCmRNA, TNF-α, and IL-βin solution group (group V) compared with blank group (groupⅠ) (P>0.05)。Conclusions:simvastatin can reduceα-ENaCmRNA expression through reducing the release of TNF-αand IL-βand increaseα-ENaCmRNA expression。It can be inferred that simvastatin may through reducing AT-Ⅱcell the release of TNF-αand IL-βand increase AT-Ⅱcell a-ENaCmRNA expression。...