机构地区:[1]济南市第二妇幼保健院检验科,山东济南271199
出 处:《中华医院感染学杂志》2023年第17期2561-2565,共5页Chinese Journal of Nosocomiology
基 金:济南市卫生健康委员会科技计划项目(2022-2-133)。
摘 要:目的探究调控Toll受体4(TLR4)对铜绿假单胞菌肺部感染模型大鼠的干预效果及作用机制.方法选取150只大鼠,30只作为空白组,其余120只建立铜绿假单胞菌肺部感染模型,将建模成功的113只大鼠分为模型组37只、TLR4上调组、TLR4下调组各38只.将10μl TLR4过表达慢病毒悬液、TLR4沉默慢病毒悬液分别注射于TLR4上调组、TLR4下调组大鼠胃部,空白组、模型组注射同剂量的生理盐水,注射2周后观察大鼠肺部病理变化,分析肺组织炎症因子、氧化应激指标水平和髓样分化因子88(Myd88)/核因子κB(NF-κB)信号通路蛋白相对表达量水平变化.结果与空白组比较,模型组、TLR4上调组、TLR4下调组TLR4相对表达量均升高(P<0.05),说明转染成功.TLR4上调组肺组织炎症因子白细胞介素(IL)-6、巨噬细胞炎性蛋白-2(MIP-2)、IL-8水平均上升(P<0.05);氧化应激指标丙二醛(MDA)、髓过氧化物酶(MPO)水平上升,总抗氧化能力(T-AOC)水平下降(P<0.05);Myd88、NF-κB蛋白相对表达量均上升(P<0.05).结论下调TLR4可减轻铜绿假单胞菌肺部感染大鼠炎性反应,改善氧化应激状况,其机制可能与Myd88/NF-κB信号通路被抑制有关.OBJECTIVE To explore the intervention effect of regulating Toll receptor 4(TLR4)on rat model with pulmonary Pseudomonas aeruginosa infection and observe the action mechanisms.METHODS Totally 150 rats were enrolled in the study,30 of which were assigned as the blank group,the rest of 120 rats were established the models of pulmonary P.aeruginosa infection,113 rats that were successfully established the models were divided into the model group with 37 rats,the up-regulated TLR4 group with 38 rats and the down-regulated TLR4 group with 38 rats.10μl of TLR4-overexpressed lentivirus suspension and TLR4-silenced lentivirus suspension were respectively injected into the stomach of rats in the up-regulated TLR4 group and the down-regulated TLR4 group.The same dose of normal saline was injected into the stomach of rats in the blank group and the model group.The pathological characteristics of lungs of the rats were observed after the injection for 2 weeks.The changes of lung tissue inflammatory factors and oxidative stress indexes as well as the relative expression levels of myeloid differentiation factor 88(Myd88)/nuclear factor-κB(NF-κB)signaling pathway proteins were observed.RESULTS The relative expression level of TLR4 of the model group,the up-regulated TLR4 group and the down-regulated TLR4 group was higher than that of the blank group(P<0.05),indicating a successful transfection.The levels of inflammatory factors interleukin(IL)-6,macrophage inflammatory protein-2(MIP-2)and IL-8 were elevated in the TLR4 up-regulated lung tissues(P<0.05);the levels of oxidative stress indexes malondialdehyde(MDA)and myeloperoxidase(MPO)were elevated;the total antioxidant capacity(T-AOC)was reduced(P<0.05).The relative expression levels of Myd88 and NF-κB proteins were elevated(P<0.05).CONCLUSION The down-regulation of TLR4 may alleviate the inflammatory response of the rats with pulmonary P.aeruginosa infection and improve the status of oxidative stress,and the action mechanisms may be associated with the inhibition of Myd88/N
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