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MyD88对小鼠肠缺血再灌注致急性肺损伤的影响
The effect of MyD88 in the acute lung injury mice of which induced by Intestinal-ischemia reperfusion.
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DOI:
作者:
陈超
chenchao
作者单位:
上海市第九人民医院
shanghai ninth people's hospital
关键词:
MyD88;缺血再灌注;肠损伤;肺损伤;Toll样受体4
MyD88;Ischemia reperfusion;Gut injury;Lung injury;Toll-1ike receptor 4
摘要:
【摘要】目的 观察MyD88对小鼠肠缺血再灌注致急性肺损伤的影响。方法 6~8周龄雄性MyD88基因敲除小鼠(MyD88-/-)及其野生型C57BL/6小鼠各24只,两组品系小鼠组内随机分为2组(n=12):假手术组(S组)及肠缺血再灌注组(I/R组)。麻醉后制备肠缺血再灌注致急性肺损伤模型。处死小鼠后开胸取肺标本,计算肺湿干重比,伊文思蓝检测肺血管通透性,H-E染色后在显微镜下观察肺组织病理学改变,ELISA检测肺组织TNF-α和IL-1β表达,RT-PCR检测TLR4mRNA表达水平。结果 与I/R组比较,MyD88+I/R组肺组织病理学损伤程度明显减轻,肺湿干重比、肺血管渗透性降低(P<0.05);肠缺血再灌注引起的肺损伤减轻,并下调肺组织TLR4 mRNA,TNF-α和IL-1β (与I/R组比较P<0.05)。结论 MyD88基因敲除可明显减轻小鼠肠缺血再灌注后肺损伤,减轻肺水肿及肺血管通透性,下调肺组织TLR4 mRNA,TNF-α和IL-1β,具有保护作用。
【Abstract】Objective To investigate the effect of MyD88 on the lung following acute lung injury(ALI) induced by intestinal ischemia-reperfusion(I/R) injury in mice. Methods Twenty-four healthy male C57BL/6 mice were randomly divided into 2 groups(n=12 each):Sham operation group(group S);intestinal I/R group(group I/R);Twenty-four healthy male MyD88-/- mice were randomly divided into 2 groups(n=12 each):Sham operation group(group S);intestinal I/R group(group I/R).Intestinal I/R injury was induced by clamping the superior mesenteric artery for 45min and the mice were sacrificed at 6 h of reperfusion.The lungs were immediately moved for microscopic examination,determination of W/D lung weight radio, EBD detectionpulmonary vascular permeability,levels of TNF-α and L-1β(by ELISA)and TLR4 mRNA expression in the lung tissue(by RT-PCR).Results Microscopic examination showed that there were collapse or consolidation alveoli,edema and infiltration of neutrophils in the lung parenchyma in C57BL/6 I/R group.Intestinal ischemia reperfusion significantly increased W/D lung weight ratio, levels of TNF-α and L-1β, and TLR4 mRNA in the lung tissu.The lung injury was significantly ameliorated in group MyD88-/- I/R as compared to group C57BL/6 I/R. MyD88-/- mice intestinal ischemia reperfusion-induced increase in W/D lung weight ratio ,levels of TNF-α and L-1βand TLR4 mRNA in the lung tissue. Conclusion MyD88 gene knock out mice were better tolerated ALI induced by intestinal ischemia reperfusion through down-regulation of TLR4 mRNA expression and decreasing levels of TNF-α and IL-1β in the lung.
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