新生小鼠高氧急性损伤中TLR4的表达

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目的探讨Toll样受体4(Toll-like receptor 4,TLR4)在新生小鼠高氧急性肺损伤中的作用。方法新生1 d的TLR4野生型(TLR4W)和TLR4突变型(TLR4M)小鼠各30只,随机分为:高氧暴露组(TLR4WO2组,TLR4MO2组)及空气对照组(TLR4WA组,TLR4MA组),每组15只。应用高浓度氧暴露72 h制作急性肺损伤小鼠模型,各组于24、48及72 h随机取5只小鼠肺组织标本,测定肺湿/干质量(W/D)比值及进行肺组织病理评分,荧光定量PCR法测定肺组织TLR4的mRNA表达,酶联免疫吸附法(ELISA)测定肺组织匀浆中白细胞介素-6(IL-6)含量。结果各TLR4WO2组肺W/D比值均较空气对照组明显增高(P<0.05)。TLR4WO2组48、72 h肺组织病理评分均明显高于空气对照组(P<0.01)。各TLR4WO2组肺组织TLR4 mRNA表达及匀浆中IL-6含量均明显高于TLR4WA组(P<0.01)。TLR4MO2组与TLR4MA组比较,上述各项指标均无明显差异(P>0.05)。结论高浓度氧能导致急性肺损伤,HALI与炎症反应有关,TLR4参与了炎症反应的发生,同时对炎症反应的维持也具有重要的作用。 Objective To investigate the role of Toll-like receptor 4 (TLR4) in hyperoxia-induced acute lung injury in neonatal mice. Methods Thirty new-born TLR4 WT (TLR4W) and TLR4 mutant (TLR4M) mice were randomly divided into three groups: hyperoxia exposure group (TLR4WO2 group, TLR4MO2 group) and air control group (TLR4WA group, TLR4MA group) , Each group of 15. The model of acute lung injury was induced by exposure to high concentration of oxygen for 72 hours. The lungs of 5 mice were randomly selected at 24, 48, and 72 hours. The lung wet / dry weight (W / D) ratio and lung tissue Pathological score and fluorescence quantitative PCR were used to detect the mRNA expression of TLR4 in lung tissue. The content of IL-6 in lung homogenate was measured by enzyme linked immunosorbent assay (ELISA). Results The lung W / D ratio of TLR4WO2 group was significantly higher than that of air control group (P <0.05). The lung histopathological scores at 48 and 72 h in TLR4WO2 group were significantly higher than those in air control group (P <0.01). TLR4WO2 group lung tissue TLR4 mRNA expression and IL-6 content were significantly higher than TLR4WA group (P <0.01). TLR4MO2 group and TLR4MA group compared to the above indicators were no significant difference (P> 0.05). Conclusions High concentration oxygen can cause acute lung injury. HALI is associated with inflammatory reaction. TLR4 is involved in the inflammatory reaction and plays an important role in the maintenance of inflammatory response.
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