灯盏花乙素对急性百草枯中毒大鼠肺部炎性介质的调控机制  

The regulatory mechanism of scutellarin on pulmonary inflammatory mediators in rats with acute paraquat poisoning

作　　者：李海燕[1] 田青 王樊 蔡纯 罗娟娟 王向阳 LI Haiyan;TIAN Qing;WANG Fan;CAI Chun;LUO Juanjuan;WANG Xiangyang(Department of Emergency,Beijing Anzhen Nanchong Hospital,Capital Medical University&Nanchong Central Hospital,Nanchong,Sichuan 637000)

机构地区：[1]首都医科大学附属北京安贞医院南充医院·南充市中心医院急诊科,四川南充637000

出　　处：《河北中医》2025年第3期437-443,共7页Hebei Journal of Traditional Chinese Medicine

摘　　要：目的探究灯盏花乙素(SCU)对急性百草枯中毒大鼠肺部炎性介质的调控机制。方法将100只大鼠随机分为对照组、模型组、SCU低剂量组(SCU-L组)、SCU高剂量组(SCU-H组)和Toll样受体4(TLR4)通路抑制剂组(TAK-242组),每组各20只。除对照组外,其余各组采用腹腔注射百草枯(30 mg/kg)构建大鼠急性百草枯肺损伤模型。造模1 h后,SCU-L组、SCU-H组和TAK-242组分别腹腔注射SCU溶液(25、50 mg/kg)1 mL和TAK-242溶液(5 mg/kg)1 mL,对照组、模型组腹腔注射0.9%氯化钠注射液1 mL,连续注射5 d。5 d后,检测肺泡灌洗液(BALF)中总细胞数、中性粒细胞数;酶联免疫吸附法(ELISA)检测BALF中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-1β、IL-4、IL-10水平;检测肺湿/干重(W/D);苏木素-伊红(HE)染色观察肺组织病理损伤及肺损伤评分;透射电镜观察肺细胞超微结构;免疫组化染色检测肺组织TNF-α、IL-6、IL-1β、IL-4、IL-10水平;蛋白免疫印记(Western blot)法检测肺组织CD68、髓过氧化物酶(MPO)、TLR4、髓样分化因子88(MyD88)、核因子-κB(NF-κB)p65、p-NF-κB p65蛋白表达水平。结果与对照组相比,模型组大鼠BALF中总细胞数、中性粒细胞数、TNF-α、IL-6、IL-1β水平升高,IL-4、IL-10水平降低,肺W/D值、肺损伤评分升高,肺组织可见明显出血和炎性浸润,肺组织中TNF-α、IL-6、IL-1β平均光密度值(MOD)及CD68、MPO、TLR4、MyD88、p-NF-κB p65/NF-κB p65蛋白水平升高,IL-4、IL-10 MOD降低(均P<0.05)。与模型组相比,SCU-L组、SCU-H组和TAK-242组大鼠BALF中总细胞数、中性粒细胞数、TNF-α、IL-6、IL-1β水平降低,IL-4、IL-10水平升高,肺W/D值、肺损伤评分降低,肺组织可见少量出血和炎性浸润,肺组织中TNF-α、IL-6、IL-1βMOD及CD68、MPO、TLR4、MyD88、p-NF-κB p65/NF-κB p65蛋白水平降低,IL-4、IL-10 MOD升高(均P<0.05),且SCU-H组和TAK-242组对上述指标的改善作用优于SCU-L组(均P<0.05),而SCU-H组和TAK-242�Objective To explore the regulatory mechanism of scutellarin(SCU)on pulmonary inflammatory mediators in rats with acute paraquat poisoning.Methods Totally 100 rats were randomly divided into Control group(1 mL 0.9%sodium chloride solution),Model group(1 mL 0.9%sodium chloride solution),low-,high-dose SCU(SCU-L,SCU-H;25 mg/kg/d,50 mg/kg/d)groups,and TAK-242,a Toll-like receptor 4(TLR4)-specific signalling inhibitor,signaling pathway inhibitor(TAK-242,5 mg/kg/d)group,with 20 rats in each group.Except for Control group,other groups were injected intraperitoneally with paraquat(30 mg/kg)to construct rat lung injury model.After 5 days,the total number of cells,and the number of neutrophils in bronchoalveolar lavage fluid(BALF)were detected.Enzyme-linked immunosorbent assay(ELISA)was used to detect levels of tumor necrosis factor-alpha(TNF-α),interleukin(IL)-6,IL-1β,IL-4,IL-10 in BALF.The hematoxylin and eosin(HE)staining was used to detect pathological damage in lung tissue.Lung injury score and lung wet weight/dry weight(W/D)ratio were detected.Transmission electron microscopy was used to observe ultrastructure of lung cells.Immunohistochemical staining was used to detect TNF-α,IL-6,IL-1β,IL-4,IL-10 levels in lung tissue.Western blot was used to detect CD68,myeloperoxidase(MPO),TLR4,myeloid differentiation factor 88(MyD88),nuclear factor-κB(NF-κB)p65,p-NF-κB p65 levels in lung tissue.Results Compared with Control group,Model group had significantly increased the total number of cells,the number of neutrophils,TNF-α,IL-6,IL-1βlevels in BALF,decreased IL-4 and IL-10 levels,increased lung W/D,lung injury score,significant bleeding and inflammatory infiltration,increased the mean optical density(MOD)of TNF-α,IL-6,IL-1βin lung tissue,CD68,MPO,TLR4,MyD88,p-NF-κB p65/NF-κB p65 protein levels,decreased IL-4 and IL-10 MOD(all P<0.05).Compared with Model group,the SCU-L group,SCU-H group and TAK-242 group had significantly decreased the total number of cells,the number of neutrophils,TNF-α,IL-6,IL-1βlevels in BA

关 键 词：灯盏花乙素 急性百草枯中毒 炎性介质 Toll样受体4/髓样分化因子88/核因子-κB信号通路 

分 类 号：R595.5[医药卫生—内科学]