Effect Of Polydatin On Oleic Acid Induced Acute Respiratory Distress Syndrome In Rats

Aims:This study is to investigate the protective effect of Polydatin(PD)against oleic acid(OA)induced acute respiratory distress syndrome(ARDS)in rats and to explore its potential mechanism.Methods:Male SD rats weighing 180-220 g were randomly divided into 5 groups(n = 6):control group,OA + saline group(OA + NS),OA + PD 15 mg/kg group(OA+ PDs),OA + PD 30 mg/kg group(OA + PDM),OA + PD 45 mg/kg group(OA +PDL),n = 6 in each group.Acute respiratory distress syndrome model was prepared by femoral vein injection of OA(100μl/kg),and rats of control group received equal volume of saline by femoral vein.Rats were sacrificed 3 hours after injection.Neutrophil numbers,protein concentration,TNF-α and IL-1β levels were determined.The protein expressions of Na+/K+-ATPase al,Na+/K+-ATPase β1,Bax,Bcl-2,Caspase-3,NF-KB-p65,Phospho-p38(p-p38),Phospho-JNK1/2/3(p-JNK1/2/3),Phospho-ERK1/2(p-ERK1/2),Phospho-PI3-kinase p85/p55(p-PI3K)in lung tissues were assessed by Western Blotting.Lung wet to dry(W/D)ratio was measured.HE staining was used to observe pathological changes and lung injury score was calculated with a semiquantitative scoring system.Immunohistochemistry was used to evaluate the expression of NF-κB-p65 in lung tissue.Results:1.OA induced lung injury in rat lungs significantly(P<0.01).PD(30 and 45 mg/kg)treatment obviously alleviated pathological changes of lung injury,inhibited the increased lung injury scores and W/D ratio levels(/P<0.05).2.OA increased PMNs and total protein in the BALF,which was significantly different from that in the control group(P<0.01),while in the medium and high-dose PD group,PMNs and total protein were significantly decreased(P<0.05).3.ELISA results showed that PD inhibited OA-induced lung inflammation in ARDS rats in a dose-dependent manner(P<0.05).4.Medium,large dose of PD significantly reversed the inhibitory effect of OA on NKA protein,and increased the expression of NKA in the lung of ARDS rats(P<0.05).5.Compared with the control group,the expression of Caspase-3 and Bax was significantly increased after OA induced,while the Bcl-2 level was decreased(P<0.01).However,PD treatment significantly down-regulated the expression of Caspase-3 and Bax and up-regulated the expression of Bcl-2.High-dose(45 mg/kg)PD treatment had the most significant effect(P<0.05).6.1n addition,treatment with PD(30,45 mg/kg)reversed the expression of MAPKs,PI3K,and NF-κB-p65 in OA-induced ARDS rat lung tissue(P<0.05).Conclusions:1.PD has the effects of inhibiting inflammatory reaction,reducing pulmonary edema and anti-apoptosis.2.PD exhibits a protective effect against OA-induced acute lung injury in rat with ARDS,which might be acted through the inhibition of the MAPKs/NF-κB or PI3K/NF-κB signaling pathways.