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甘草酸二铵对脂多糖所致小鼠急性肺损伤保护作用的研究 摘要 目的:探究甘草酸二铵(GA)对脂多糖(LPS)所致小鼠急性肺损伤(ALI)的保护作用及其机制。 方法:将40只SD大鼠随机分为对照组(C组)、模型组(M组)、低剂量GA组(L组)和高剂量GA组(H组),除C组外其余组细胞外基质(ECM)通过气管注入LPS建立ALI模型。L、H组分别给予10mg/kg、30mg/kgGA处理。24小时后记录大鼠体重、血气、肺湿重/干重比和超表观结构。 结果:ALI大鼠模型建立后,M组体重下降、肺湿重/干重比和动脉血气的肺泡动脉氧分压差(PAO2/FiO2)均明显高于C组(P<0.05)。低、高剂量GA均能显著减轻ALI大鼠的上述指标异常,且高剂量GA组显著优于低剂量GA组(P<0.05),提示GA对ALI大鼠的损伤具有保护作用。肺组织超表观结构显示L、H组肺泡充气减少,肺泡间隔变宽和破坏明显改善。L组肺泡浸润炎细胞多见,而H组抑制了炎症细胞浸润迅速,肺泡变态反应显著减轻。GA处理可减轻LPS对肺泡壁的破坏、减轻炎症反应、减少白细胞浸润。 结论:甘草酸二铵对LPS所致ALI大鼠模型有良好的保护作用,其机制可能与减轻肺泡壁破坏、减少炎症反应和白细胞浸润有关。 关键词:甘草酸;脂多糖;急性肺损伤;大鼠;保护作用 Abstract Objective:ToexploretheprotectiveeffectandmechanismofGlycyrrhizinicAcid(GA)onlipopolysaccharide(LPS)-inducedacutelunginjury(ALI)inmice. Methods:40SDratswererandomlydividedintothecontrolgroup(Cgroup),themodelgroup(Mgroup),thelow-doseGAgroup(Lgroup)andthehigh-doseGAgroup(Hgroup).ECMwasinjectedintothetracheatoestablishanALImodel.TheLandHgroupsweretreatedwith10mg/kgand30mg/kgGA,respectively.After24hours,theweight,bloodgas,lungwet-to-dryweightratioandultrastructuralchangesofthelungswererecorded. Results:AftertheALImodelwasestablished,theMgroupshowedasignificantdecreaseinbodyweight,anincreaseinthelungwet-to-dryweightratio,andanincreaseinthepulmonaryarteryoxygenpressuredifference(PAO2/FiO2)comparedwiththeCgroup(P<0.05).Bothlow-andhigh-doseGAcouldsignificantlyreducetheabovementionedabnormalindicatorsofALIrats.Moreover,thehigh-doseGAgroupwassignificantlybetterthanthelow-doseGAgroup(P<0.05),suggestingthatGAhasaprotectiveeffectontheinjuryofALIrats.TheultrastructuralchangesoflungtissueinLandHgroupsshowedthatthealveolarinflationwasreduced,thealveolarseptumwaswidenedanddamaged,andthepathologicalchangeswereimproved.Lgroupshowedahighlevelofinflammatorycellinfiltration,whileHgroupinhibitedtherapidinfiltrationofinflammatorycells,andsignificantlyreducedpulmonaryallergicreactions.GAtreatmentcanalleviatelungtissuedamage,reducetheinflammatoryreaction,andreduceleukocyteinfiltrationcausedbyLPS. Conclusion:GAhasagoodprotectiveeffectonthe