【作者】 傅水桥； 骆小倩； 张绍阳； 章渭方；

【机构】 浙江大学医学院附属第二医院SICU； 浙江大学医学院附属第一医院；

【摘要】 目的研究晚期糖基化终末产物受体(RAGE)抗体对脂多糖(LPS)诱导的小鼠肺损伤的保护作用。方法将50只C57BL/6小鼠分成健康对照组(10只)和LPS诱导的急性肺损伤组(40只),其中LPS诱导组分成四个亚组,每组10只,分别为:安慰剂治疗组,10μgRAGE抗体处理组,20μg RAGE抗体处理组和50μg RAGE抗体处理组。通过静脉注射LPS建立小鼠急性肺损伤(ALI)模型。采用HE染色观察不同组小鼠肺组织病理学改变并对肺损伤严重程度进行评分;采用湿/干重比(W/D)分析小鼠肺水肿程度;采用MPO活性以及肺泡灌洗液(BALF)中浸润细胞计数分析小鼠肺组织炎症反应程度;采用ELISA的方法检测不同组小鼠肺泡灌洗液中炎症因子TNF-α、IL-6、IL-1和MCP-1的水平。结果小鼠在给予LPS静脉注射后,肺组织出现显著病理学改变以及较高的肺损伤评分,同时肺组织W/D的比值也显著升高,同时肺组织中MPO活性以及BALF中浸润的炎症细胞数目也显著升高,且这些差异都具有显著统计学意义(P<0.05)。但是与LPS诱导组相比,给予不同剂量RAGE抗体处理组小鼠肺损伤程度出现显著改善,包括肺组织损伤程度评分、W/D比值、MPO活性以及炎症细胞浸润数目,同时RAGE抗体的处理还显著抑制了BALF中炎症因子的分泌水平,以上差异均具有显著性统计下意义(P<0.05)。结论:RAGE抗体可以通过抑制小鼠肺组织中炎症反应程度有效的改善LPS诱导的小鼠ALI情况,包括肺部炎症以及肺水肿程度。更多还原

【Abstract】 Objective:To investigate the protective effect of RAGE antibody on LPS-induced acute lung injury in mice.Methods:A total of 50 C57 BL6 mice were randomly divided into five groups:the health control group(n=10,no treatment);the PBS treated ALI group(n=10),the mice were treated with LPS to induce ALI,and then treated with PBS by tail vein injection;10 μg RAGE antibody treated group(n=10),mice were treated with LPS to induce ALI,and the treated with 10 μg RAGE antibody by tail vein injection;20 μg RAGE antibody treated group(n=10),mice were treated with LPS to induce ALI,and the treated with 20 μg RAGE antibody by tail vein injection;50 |JLg RAGE antibody treated group(n=10),mice were treated with LPS to induce ALI,and the treated with 50 μg RAGE antibody by tail vein injection.Then the lung wet to dry ratio,MPO activity,infiltrated inflammatroy cells and the concentrations of inflammatory cytokines in BALF were measured to evaluate the effect of RAGE antibody on LPS-induced ALI.Results:RAGE antibody treatement obviously decreased the wet to dry ratio,MPO antivity,infiltrated inflammatory cells and the levels of inflammatory cytokines compared with the PBS treated ALI group.Meanwhile,RAGE antibody treatment significantly attenuated the lesions caused by LPS induction with a dosage-dependent manner.Conclusion:RAGE antibody has a potentially therapeutic effect on the LPS-induced acute lung injury in mice by inhibiting the inflammatory responses stimulated with the activation of RAGE-mediated signal pathway in mice.更多还原