Diosmetin Promotes The Repair Of The Pulmonary Epithelial Cells Induced By Lipopolysaccharide

Acute lung injury(ALI)is a common critical disease,which is characterized by pulmonary inflammation and pulmonary edema caused by various pathogenic factors and has a high mortality in clinic.It has been well documented that pulmonary epithelial cells damage and repair play a central role in the pathogenesis of ALI because of its barrier function.Nevertheless,the leading compounds that effectively accelerate epithelial cell repair and improve barrier dysfunction in ALI are largely unknown.Our previous works indicated that diosmetin showed strong anti-inflammatory activity in a cell model of inflammation treated with LPS by determining nitric oxide(NO)content,but the role of diosmetin in the repair of pulmonary epithelial cells needed to be explored.Here,we design to investigate the roles of diosmetin in the repair of pulmonary epithelial cells and its associated molecular mechanisms.Data from MTT,Ed U assays and wound healing experiment revealed that diosmetin promoted the proliferation and migration of BEAS-2B(a human pulmonary vascular endothelial cells)challenged by LPS.TEER and FITCDextran experiments demonstrated that diosmetin improvd the barrier dysfunction by inhibiting the decrease of TEER decrease and the leakage of FITC-Dextran in LPS-treated BEAS-2B cells.Western blotting indicated that diosmetin evidently inhibited the decrease of tight junction related proteins Zonula occludens-1(ZO-1)caused by LPS in BEAS-2B cells.Meanwhile,to explore the role of diosmetin in vivo,we constructed an ALI animal model by LPS inhalation.Our data indicated that diosmetin obviously reduced the level of tumor necrosis factor-α(TNF-α)in serum,decreased the W/D ratio of lung tissue,attenuated the number of lymphocytes,monocytes and neutrophils in BALF,inhibited the infiltration of inflammatory cells in trachea,and improved the permeability of lung tissue of ALI mice.H&E staining showed that diosmetin alleviated the pathological injuries,including pulmonary wall thickening,alveolar wall collapses,and inflammatory cell infiltration,etc.in LPS-treated C57BL/6 mice.Totaken together,diosmetin showed an interesting characteristic to improve the barrier dysfunction by promoting the proliferation of lung epithelial cells,upregulating the expression of barrier function-related proteins,and alleviating the edema and inflammatory response of lung tissues in ALI mice.All these findings indicated that diosmetin would be helpful to accelerate the repair of pulmonary epithelial cells and improve the barrier function in ALI.