The Prevention Of Chrysin On LPS-induced Acute Lung Injury In Mice

Background:Acute lung injury and its severe stage,acute respiratory distress syndrome,were a major clinical problem that characterized by severe hypoxemia,airway dysfunction,and uncontrolled inflammatory responses in the lungs.In the past decades,the mortality of ALI remained high.There are still few effective measures or drugs to treat it.Therefore,it is urgent to seek new drugs to treat ALI.Chrysin,a kind of natural flavonoid compound extracted from plant and vegetables,has many biological effects including supression of lung inflammation via downregulation LPS-induced production of inflammatory cytokines.Studies have shown that the endoplasmic reticulum stress play crucial role in acute lung injury.LPS-induced mice ALI model,a widely accepted animal model of lung injury,was used in our study.We aimed to investigate the protective effects of Chrysin on LPS-induced ALI and clarify the underlying mechanisms.Objectives:1.To observe the protective effects of Chrysin on LPS-induced acute lung injury in mice.2.To demonstrate whether Chrysin could ameliorate LPS-induced acute lung injury via inhibition of endoplasmic reticulum stress.Methods:Male ICR mice were randomly divided into 5 groups with 42 mice in each group.control group :were given equal volume PBS;LPS group:LPS(3 mg/kg)was administered intratracheally to induce ALI;Low-dose chrysin group(CHR-L group);High-dose chrysin group(CHR-H group);ERS inhibitor group(4-PBA).6 h after LPS treatment,lung tissue histological changes was assessed by HE staining.Alveolar capillaries permeability was determined by Evans blue staining and BCA assay.The ratio of the wet lung to the dry lung was calculated to assess tissue edema.The activity of MPO and antioxidative function were determined in the lung tissue by kits.The levels of proinflammatory cytokines in BALF and lung tissues were determined by ELISA kits.The protein levels of ERS markers and TXNIP/NLRP3 in lung tissues was detected by Western Blot.Results:Under the light microscope,no evident histological alteration was observed in lung sections of the control group.However,lung sections of LPS group showed significant pathological changes,such as inflammatory cells infiltration,pulmonary congestion,and thickening of the alveolar wall.Pretreatment of Chrysin markedly ameliorated LPS-induced lung injury and lung vascular leakage.Pretreatment of Chrysin also significantly inhibited LPS-induced lung W/D ratio,activity of MPO and the levels of inflammatory cytokines IL-1?,IL-6 and TNF-? production in lung tissue and BALF.Furthermore,pretreatment of Chrysin and 4-PBA significantly down-regulated LPS-induced GRP78,ATF6 and p-IRE1/IRE1 protein expression,reduced MDA content and improve the activity of SOD and GSH-Px,and decreased expressions of NLRP3 and TXNIP in the lung tissues.Our results suggested that Chrysin and 4-PBA could inhibition of LPS-induced ERS and oxidative stress,suppression of NLRP3/TXNIP signaling pathway.Conclusions:The chrysin could alleviate LPS induced-acute lung injury may be associated with inhibition of ERS and then attenuate oxidative stress injury,down-regulation ofTXNIP / NLRP3 and reduced the production of proinflammatory cytokines.