木犀草素抑制ROS/TXNIP/NLRP3信号通路激活对小鼠急性呼吸窘迫综合征的改善作用  

Improvement effect of luteolin on acute respiratory distress syndrome by inhibiting ROS/TXNIP/NLRP3 signaling pathway activation in mice

作　　者：曲海新[1] 袁二伟[1] 郭卫平[2] 张雅静[1] 马文霞[2] 吴丹 QU Haixin;YUAN Erwei;GUO Weiping;ZHANG Yajing;MA Wenxia;WU Dan(Department of Neonatology,First Affiliated Hospital,Hebei North University,Zhangjiakou 075000,China;Department of Pediatrics,First Affiliated Hospital,Hebei North University,Zhangjiakou 075000,China)

机构地区：[1]河北北方学院附属第一医院新生儿科,河北张家口075000 [2]河北北方学院附属第一医院儿科,河北张家口075000

出　　处：《吉林大学学报（医学版）》2022年第3期676-683,共8页Journal of Jilin University：Medicine Edition

基　　金：河北省卫健委医学科学研究课题计划项目(20211818)。

摘　　要：目的:探讨木犀草素调控活性氧(ROS)/硫氧还蛋白结合蛋白(TXNIP)/NOD样受体相关蛋白3(NLRP3)信号通路激活对小鼠急性呼吸窘迫综合征(ARDS)的改善作用。方法:60只SD小鼠随机分为对照组、模型组、木犀草素(20 mg·kg^(-1))组、邻苯三酚(PG)(75 mg·kg^(-1))组和木犀草素(20 mg·kg^(-1))+PG(75 mg·kg^(-1))组,每组12只。除对照组外,其他组小鼠采用气管滴注脂多糖(LPS)溶液的方法建立ARDS模型,对照组小鼠气管滴注等量生理盐水。称量各组小鼠右肺湿质量和干质量,并计算湿质量/干质量(W/D)比值,检测各组小鼠动脉血氧分压(PaO_(2)),HE染色观察各组小鼠肺组织病理形态表现,检测各组小鼠吸气阻力(Ri)、每分钟通气量(MV)和呼气峰流速(PEF),检测各组小鼠肺组织中ROS、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)水平及血清白细胞介素18(IL-18)、白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)水平,Western blotting法检测各组小鼠肺组织中TXNIP、caspase-1、caspase-4和NLRP3蛋白表达水平。结果:与对照组比较,模型组小鼠肺泡壁变厚,肺泡塌陷变形,肺间质水肿伴有大量炎性细胞浸润,肺组织有严重病理损伤,W/D比值,Ri,血清IL-18、IL-1β及TNF-α水平,肺组织中ROS水平及TXNIP、caspase-1、caspase-4和NLRP3蛋白表达水平升高(P<0.05);MV、PEF、PaO_(2)和肺组织中GSH-Px及CAT水平降低(P<0.05)。与模型组比较,木犀草素组小鼠肺组织病理损伤均有所改善,W/D比值,Ri,血清IL-18、IL-1β及TNF-α水平,肺组织中ROS水平和TXNIP、caspase-1、caspase-4及NLRP3蛋白表达水平均降低(P<0.05),MV、PEF和PaO_(2)及肺组织中GSH-Px和CAT水平均升高(P<0.05);PG组小鼠肺组织病理损伤均加重,W/D比值,Ri,血清IL-18、IL-1β及TNF-α水平,肺组织中ROS水平及TXNIP、caspase-1、caspase-4和NLRP3蛋白表达水平均升高(P<0.05),MV、PEF和PaO_(2)及肺组织中GSH-Px和CAT水平均降低(P<0.05)。结论:木犀草素可通过�Objective:To investigate the improvement effect of luteolin in the mice with acute respiratory distress syndrome(ARDS)by regulating the activation of reactive oxygen species(ROS)/thioredoxin binding protein(TXNIP)/NOD like receptor associated protein 3(NLRP3)signaling pathway.Methods:A total of 60 SD mice were randomly divided into control group,model group,luteolin(20 mg·kg^(-1))group,pyrogallol(PG)(75 mg·kg^(-1))group,luteolin(20 mg·kg^(-1))+PG(75 mg·kg^(-1))group,and there were 12 mice in each group.Besides control group,the mice in the other groups were instilled with lipopolysaccharide(LPS)solution through the trachea to establish the ARDS models,and the mice in control group were instilled with the same amount of normal saline through the trachea.The wet weights and dry weights of right lung tissue of the mice in various groups were weighed,and ratios of the wet weight/dry weight(W/D)of the mice in various were caculated;the arterial blood oxygen pressure(PaO_(2))was measured;the pathomorphology of lung tissue of the mice in various groups was observed by HE staining;the inspiratory resistance(Ri),minute ventilation(MV)and peak expiratory flow rate(PEF)of the mice in various groups were detected;the levels of ROS,glutathione peroxidase(GSH-Px),catalase(CAT)in lung tissue and levels of serum interleukin-18(IL-18),interleukin-1β(IL-1β)and tumor necrosis factorα(TNF-α)of the mice in various groups were determined;the expression levels of TXNIP,caspase-1,caspase-4 and NLRP3 proteins in lung tissue of the mice in various groups were detected by Western blotting method.Results:Compared with control group,the alveolar walls of the mice in model group became thicker,the alveoli collapsed and deformed,the pulmonary interstitial edema was accompanied by a large number of inflammatory cell infiltration,and the lung tissue had the severe pathological damage;the W/D ratio,Ri,serum IL-18,IL-1βand TNF-αlevels,the level of ROS and the expression levels of TXNIP,caspase-1,caspase-4,and NLRP3 proteins in lung tissu

关 键 词：木犀草素 活性氧 硫氧还蛋白结合蛋白 NOD样受体相关蛋白3 急性呼吸窘迫综合征 

分 类 号：R563.8[医药卫生—呼吸系统]