脂质体前列腺素E1对重症肺炎大鼠炎性介质的调控机制  

Regulation mechanism of liposome prostaglandin E1 on inflammatory mediators in rats with severe pneumonia

作　　者：赵申 李俊杰 ZHAO Shen;LI Junjie(Department of Pediatrics,Affiliated Hospital of Hubei University of Arts and Sciences,Xiangyang Central Hospital,Xiangyang 441000,China)

机构地区：[1]湖北文理学院附属医院/襄阳市中心医院儿科,襄阳441000

出　　处：《西北药学杂志》2022年第2期67-71,共5页Northwest Pharmaceutical Journal

基　　金：湖北省卫生健康委员会基金项目(编号:WJ2019F088)。

摘　　要：目的探究脂质体前列腺素E1(lip-PGE1)对重症肺炎大鼠炎性介质的调控机制。方法选取45只雄性SD大鼠,随机分为对照组、模型组和lip-PGE1组,每组15只,模型组和lip-PGE1组采用气管穿刺肺炎克雷伯菌制成重症肺炎模型,lip-PGE1组尾静脉注射1μg·kg^(-1)的lip-PGE1,连续注射5 d,对照组和模型组注射等量生理盐水。分别于注射后第7、9和11天收集肺泡灌洗液(bronchoalveolar lavage fluid,BALF),检测BALF中的总细胞数、中性粒细胞数、白细胞介素-6(interleukin-6,IL-6)、IL-1β和肿瘤坏死因子α(tumor necrosis factorα,TNF-α)水平,用HE染色观察大鼠肺组织的病理变化,用蛋白质印迹法检测肺组织中核因子κB(nuclear factorκB,NF-κB)P65、NF-κB抑制蛋白(NF-κB inhibitory protein,IκB)、Toll样受体4(toll-like receptor 4,TLR4)和髓样分化因子88(myeloid differentiation factor 88,MyD88)的表达水平,用免疫荧光法观察NF-κB P65的核迁移情况。结果药物注射后第7、9和11天,模型组和lip-PGE1组BALF中的细胞总数、中性粒细胞数逐渐增加,IL-6、IL-1β和TNF-α的表达水平逐渐上升;与模型组比较,lip-PGE1组细胞总数、中性粒细胞数、IL-6、IL-1β、TNF-α、p-P65/P65、TLR4、MyD88和NF-κB P65阳性细胞数均显著降低,p-IκB/IκB水平升高(P<0.05)。结论lip-PGE1可有效抑制重症肺炎大鼠的炎症反应,减轻肺组织损伤,其作用机制可能与阻滞TLR4/NF-κB信号通路有关。Objective To explore the regulation mechanism of liposome prostaglandin E1(lip-PGE1)on inflammatory mediators in rats with severe pneumonia.Methods 45 male SD rats were enrolled and randomly divided into control group,model group and lip-PGE1 group,15 cases in each group.In model group and lip-PGE1 group,severe pneumonia models were prepared by trachea puncture of Klebsiella pneumoniae.The lip-PGE1 group injected with 1μg·kg^(-1) lip-PGE1 through tail vein for 5 d.The control group and model group were injected with the same volume of normal saline.On the 7th,9th and 11th day after injection,the bronchoalveolar lavage fluid(BALF)was collected to detect total cells count,neutrophils count,interleukin(IL)-6,IL-1βand tumor necrosis factorα(TNF-α).The pathological changes of lung tissues were observed by HE staining.The expressions of nuclear factorκB(NF-κB)P65,NF-κB inhibitory protein(IκB),toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88)were detected by Western blot.The nuclear migration of NF-κB P65 was observed by immunofluorescence method.Results On the 7th,9th and 11th day after injection,the total cells count,neutrophils count,IL-6,IL-1βand TNF-αwere gradually increased in model group and lip-PGE1 group.Compared with model group,the total cells count,neutrophils count,IL-6,IL-1β,TNF-α,number of p-P65/P65,TLR4,MyD88 and NF-κB P65 positive cells were significantly decreased,while the level of p-IκB/IκB was increased in lip-PGE1 group(P<0.05).Conclusion The lip-PGE1 can effectively inhibit inflammatory response in rats with severe pneumonia,and reduce damage in lung tissues.Its action mechanism may be related to blocking TLR4/NF-κB signaling pathway.

关 键 词：脂质体前列腺素E1 重症肺炎 肺炎克雷伯菌 炎性介质 TLR4/NF-κB信号通路 

分 类 号：R965[医药卫生—药理学]