Study On Protective Effect And Mechanism Of Ferulic Acid On Lipopolysaccharide-induced Trachea And Lung Injury In Mice

Objective:Trachea injury and acute lung injury(ALI)are hackneyed clinical diseases,and there is no effective treatment method currently.Epithelial sodium channels(ENa C)belongs to rate-limiting step of alveolar fluid clearance,therefore,they are particularly crucial for maintaining and regulating the balance of fluid transport in the respiratory system.Ferulic acid(FA),which exists widely in Angelica,Chuanqiong and Asafetida,has anti-oxidation,anti-inflammatory and anti-edema effects,providing the possibility for the treatment of related diseases ailment.Therefore,increasing the expression of ENa C would play important roles in alleviating trachea injury and ALI after treating with FA.This research aims to explore the effects and mechanism of FA on ENa C expressed in the trachea and alveolar epithelium.Methods:1.HE staining experiment was used to prove the effect of FA on pathology of lipopolysaccharide(LPS)-induced trachea injury and ALI model mice.2.The effects of FA on the clearance of lung fluid in mice were investigated by wet/dry ratio of lung and alveolar fluid clearance rate tests.3.CCK-8 method was applied to explore the influence of different concentrations of FA on the proliferation ability of H441 cells.4.The effect of FA on short-circuit current of mouse tracheal epithelial cells(MTECs)was analyzed by Ussing chamber technique.5.The role of FA in regulating ENa C of damaged tissues and epithelial cells was investigated by Western Blot and q RT-PCR.6.Contents of c GMP in lung homogenates were detected by ELISA Kit.7.Inhibitor of c GMP and specific small interfencence RNA targeting PKGII were applied to explore whether FA affected the expression of total ENa C protein of MTECs and H441 via the c GMP/PKGII signal pathway.Results:1.FA could ameliorate the physical changes of trachea and lung injury,increase the fluid clearance rate and reduce the wet-to-dry ratio of lung in mice.2.When the concentration of FA reached 200 μM,the proliferation ability of H441 cells reached the maximum.3.The decrease of amiloride-sensitive currents in MTECs affected by LPS could be reversed by FA.4.Western Blot and q RT-PCR were used to explore the roles of FA in regulating ENa C in damaged tissues and epithelial cells.4.FA interdicted the reduction of c GMP in lung homogenates induced by LPS.5.Inhibitor of c GMP and small specific interference RNA of PKGII attenuated the impact of FA on ENa C in MTECs as well as H441 cells.Conclusions:cGMP/PKGII signal pathway was involved in regulation of LPS-induced ENa C by FA,which provided a possibility for the treatment of tracheal and lung injury in mice.