| Objective:1.To research whether quercetin plays a protective role in lipopolysaccharide(LPS)-induced acute lung injury.2.To research whether quercetin can attenuate LPS-induced acute lung injury(ALI)byaffectingthe activity of Nrf-2/ARE signaling pathway.Methods:The rat were divided into the following six groups(n = 7 each): control group,LPS model group,quercetin low dose(50mg/Kg QUE-L)treatment group;quercetin medium dose(100mg/Kg QUE-L)treatment group;quercetin high dose(200mg/Kg QUE-H)treatment group;dexamethasone(5mg/Kg DEX)treatment group.In the treatment group,quercetin was intraperitoneally injected 30 min before modeling,LPS(5mg/Kg)was injected into tail vein in model group and treatment group,the control group was replaced by saline injection.After 6 hours of modeling,lung histology was observed by HE staining.The ratio of wet weight to dry weight of lung tissue was calculated to analyze the degree of pulmonary edema and blood gas analysis was performed.The lung cancer MPO,MDA,SOD activity and bronchoalveolar lavage fluid(BALF)protein were detected by the kit.The levels of pro-inflammatory factors(IL-1?,TNF-?)in lung tissue were detected by ELISA kit and The activity of MPO,MDA and SOD in lung tissue was detected by kit.The content of pro-inflammatory factors(IL-1?,TNF-?)was detected by ELISA kit.The Nrf-2 signalpathway-associated proteins(Nrf-2,HO-1)and Trx-1,NF-kB/p65,ICAM-1 in lung tissue was detected by Western Blot.Results:1.Quercetindownregulate the increase of W/D in lung tissue induced by LPS: After pretreatment with different doses of quercetin,it was found that quercetin downregulated the increase of W/D in lung tissue induced by LPS,especially in the high dose group of quercetin(200 mg/Kg QUE-H).2.Quercetin alleviates the morphological changes of lung tissue induced by LPS in rats: Lung tissue sections of rats in each group were observed under light microscopy,tissue edema,pulmonary cell swelling and vascular atrophy were observed in LPS group,and no significant histological changes were observed in control group.After quercetin pretreatment,the above symptoms were improved,which showed that pulmonary interstitial edema improved significantly,and the lung tissue structure was close to normal,especially in the high dose group of quercetin(200mg/Kg QUE-H).The same conclusion was reached in the lung tissue injury score.3.Quercetin improves LPS-induced changes in blood gas analysis in rats: Compared with the control group,the Pa O2 in LPS group decreased and Pa CO2 increased.Quercetin pretreatment can increase Pa O2 and decrease Pa CO2,especially in the high dose group of quercetin(200 mg/Kg QUE-H).4.Quercetin improves the changes of oxidative stress protein in lung tissue of LPS-induced rats: Compared with the control group,MDA content and MPO activity in lung tissue of LPS-induced rats increased,while SOD activity decreased.Quercetin pretreatment could downregulate MDA content,MPO activity and upregulate SOD activity,especially in the high dose group of quercetin(200mg/Kg QUE-H),and there was no significant difference between the high dose group of quercetin and the dexamethasone group.5.Quercetin downregulates the expression of proinflammatory factors in rat lung tissue induced by LPS: After pretreatment with different doses of quercetin,it was found that quercetin downregulated the increase of IL-1beta and TNF-alpha induced by LPS,and was more obvious in the high dose group of quercetin(200mg/Kg QUE-H),but weaker in the dexamethasone group.6.Quercetin improves the expression of Nrf-2/ARE signaling pathway-related proteins in LPS-induced lung tissue of rats: After pretreatment with different doses of quercetin,it was found that quercetin further increased the expression levels of Nrf-2,Trx-1 and HO-1 induced by LPS,and decreased the expression levels of NF-B/p65 and ICAM-1,especially in the high dose group of quercetin(200mg/Kg QUE-H).Conclusion:1.Quercetin has protective effect on LPS-induced ALI in SD rats.2.The protective effect of quercetin may be related to its influence on the activity of Nrf-2/ARE signaling pathway,down-regulation of the expression levels of NF-B/p65 and ICAM-1 proteins,and ultimately reduction of the release of pro-inflammatory factors. |
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