赤藓糖醇在脂多糖诱导的小鼠急性肺损伤中的保护作用研究  

Protective effect of erythritol on lipopolysaccharide-induced acute lung injury in mice

作　　者：张曦月 张玉国 罗嫚 ZHANG Xiyue;ZHANG Yuguo;LUO Man(Department of Respiratory Medicine,Affiliated Hangzhou First People's Hospital,Zhejiang University School of Medicine,Hangzhou 310006,China;不详)

机构地区：[1]浙江大学医学院附属杭州市第一人民医院呼吸内科,杭州310006 [2]梅河口市中医院内一科

出　　处：《浙江医学》2023年第17期1818-1822,1857,I0005,共7页Zhejiang Medical Journal

基　　金：国家自然科学基金项目(82000006);浙江省自然科学基金项目(LQ20H010003)。

摘　　要：目的探讨赤藓糖醇(Ery)对脂多糖(LPS)诱导的小鼠急性肺损伤(ALI)的保护作用及机制。方法采用随机抽签法将40只小鼠分为空白对照组(NT组)、药物对照组(Ery组)、模型组(LPS组)和治疗组(LPS+Ery组),每组10只。Ery组及LPS+Ery组小鼠胃部灌注Ery(100 mg/kg Ery粉末溶于100μL 0.9%氯化钠注射液),1次/d,共6 d;NT组及LPS组小鼠胃部灌注100μL 0.9%氯化钠注射液。6 d后,LPS组及LPS+Ery组小鼠鼻内滴注LPS(1.25 mg/kg LPS粉末溶于20μL PBS)诱导小鼠ALI,NT组及Ery组小鼠鼻内滴注20μL PBS。12 h后,每组随机选取5只小鼠,获取新鲜肺组织,采用肺组织湿重/干重(湿/干)比值和HE染色评估肺组织损伤情况,检测肺组织髓过氧化物酶(MPO)活性,采用Western blot法检测炎症相关蛋白磷酸化p65(p-p65)蛋白表达水平。每组剩余的5只小鼠进行肺泡灌洗,获取肺泡灌洗液,采用ELISA法检测小鼠肺泡灌洗液中炎症因子IL-6水平。应用AutoDock工具及PyMOL软件将Ery分子与p65蛋白进行对接模拟。结果与NT组比较,LPS组小鼠可见肺组织损伤,肺组织损伤评分、肺组织湿/干比值、肺泡灌洗液中IL-6水平、肺组织中MPO活性及p-p65蛋白表达水平均升高,差异均有统计学意义(均P<0.05);与LPS组比较,LPS+Ery组小鼠肺损伤程度明显减轻,肺组织损伤评分、肺组织湿/干比值、小鼠肺泡灌洗液中IL-6水平、肺组织中MPO活性及p-p65蛋白表达水平均降低,差异均有统计学意义(均P<0.05)。此外,Ery分子与p65蛋白具有较强的结合作用。结论Ery可以减轻LPS诱导的ALI小鼠肺损伤的严重程度,降低ALI小鼠炎症因子的表达水平,并通过抑制p65信号的激活抑制炎症反应,从而发挥对LPS诱导的ALI小鼠的保护作用。Objective To investigate the protective effect and mechanism of erythritol(Ery)on lipopolysaccharide(LPS)-induced acute lung injury in mice.Methods Forty BALB/C male mice were randomly divided into no treatment group(NT group),drug control group(Ery group),model group(LPS group)and Ery treatment group(LPS+Ery group)with 10 mice in each group.Ery group and LPS+Ery group were given a gavage of Ery 100 mg/kg in 100μL 0.9%normal saline q.d for 6 d,and same volume of normal saline was given to NT group and LPS group.After 6 d,mice in LPS group and LPS+Ery group were infused intranasally with 1.25 mg/kg LPS in 20μL PBS to induce acute lung injury,while same volume of PBS was given to mice in NT group and Ery group.After 12 h,5 mice in each group were randomly selected were sacrificed to obtain fresh lung tissue samples.The wet/dry ratio of lung tissue and HE staining were performed to evaluate lung injury,and the activity of myeloperoxidase(MPO)in lung tissue was detected.The expression level of p65 was detected by Western blot.The remaining 5 mice in each group underwent alveolar lavage,and the expression level of IL-6 protein in the alveolar lavage fluid was detected by ELISA.AutoDock tool and PyMOL software were used to simulate the docking between Ery molecule and p65 protein.Results Compared with NT group,LPS group showed lung tissue injury,and the lung tissue injury score,lung tissue wet/dry ratio,IL-6 level in mice alveolar lavage fluid,MPO activity in lung tissue and p-p65 protein expression level were significantly increased(all P<0.05).Compared with LPS group,the degree of lung injury in LPS+Ery group was significantly alleviated;and the lung tissue injury score,lung tissue wet/dry ratio,IL-6 protein level in mice alveolar lavage fluid,MPO activity in lung tissue and p-p65 protein expression level were significantly reduced(all P<0.05).The bioinformational analysis showed that Ery molecule had a strong binding effect with p65 protein.Conclusion Ery can alleviate the severity of acute lung injury,inhibit the

关 键 词：赤藓糖醇 脂多糖 急性肺损伤 

分 类 号：TS201.4[轻工技术与工程—食品科学]