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GSDMD基因敲除对内毒素所致小鼠急性肺损伤的保护作用
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GSDMD基因敲除对内毒素所致小鼠急性肺损伤的保护作用
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Journal Article
GSDMD基因敲除对内毒素所致小鼠急性肺损伤的保护作用
2020
Overview
R363; 目的 探讨GSDMD基因对内毒素所致小鼠急性肺损伤(ALI)的作用.方法 20只野生型C57BL/6小鼠和20只GSDMD基因敲除C57BL/6小鼠随机分为野生型对照组(WT-sham组)、野生型ALI组(WT-ALI组)、基因敲除型对照组(KO-sham组)及基因敲除型ALI组(KO-ALI组),每组10只.ALI组经气管滴入1 mg/kg脂多糖(LPS)制备小鼠ALI模型,对照组气管滴入等体积的PBS溶液.造模成功后取肺组织和肺泡灌洗液(BALF).肺组织行HE染色,光镜下完成肺损伤半定量评分,并测量肺组织湿/干重比(W/D);采用BCA法检测BALF中总蛋白含量,ELISA法检测BALF中TNF-α、IL-1β和IL-6水平;Western blotting检测BALF和肺组织中焦亡相关蛋白的表达.结果 与WT-ALI组相比,KO-ALI组小鼠肺损伤半定量评分及肺组织W/D均明显降低(P<0.01),BALF中总蛋白含量以及TNF-α、IL-1β、IL-6水平亦明显降低(P<0.05或P<0.01).基因敲除型小鼠未见GSDMD蛋白的表达和活化.野生型小鼠和基因敲除小鼠接受LPS处理后,caspase-1和caspase-11蛋白表达均上调(P<0.01).结论 经气管滴入LPS可以诱导小鼠肺内出现GSDMD蛋白的表达和活化,而GSDMD基因敲除有助于降低肺组织炎症水平并减轻肺组织损伤程度.
Publisher
解放军总医院第六医学中心重症医学科,北京 100048%解放军总医院第六医学中心卫勤部,北京 100048%新华通讯社门诊部,北京 100803
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