萝卜硫素抑制慢性阻塞性肺疾病大鼠炎症反应及减轻气道重塑的基础研究  

Basic Study on Inhibitory Effect of Sulforaphane on Inflammatory Response and Alleviation of Airway Remodeling in COPD Rats

作　　者：连雪梅 高永红[1] 张长洪[2] 乔溪莹[3] LIAN Xue-Mei;GAO Yong-Hong;ZHANG Chang-Hong;QIAO Xi-Ying(Beijing Aerospace General Hospital,Beijing 100000,China;The First Affiliated Hospital of Hebei North University,Zhangjiakou 075061 Hebei,China;Huguosi Hospital of Traditional Chinese Medicine Affiliated to Beijing University of Traditional Chinese Medicine,Beijing 100000,China)

机构地区：[1]北京航天总医院,北京100000 [2]河北北方学院附属第一医院,河北张家口075061 [3]北京中医药大学附属护国寺中医医院,北京100000

出　　处：《广州中医药大学学报》2024年第1期185-191,共7页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：中国航天科技集团有限公司第一研究院技术创新基金资助项目(编号:YC202002);河北省卫建委医学科学研究基金资助项目(编号:20180868);国家中医药管理局国家中医临床研究基地业务建设科研专题课题项目(编号:JDZX2015246)。

摘　　要：【目的】探讨萝卜硫素对慢性阻塞性肺疾病(COPD)大鼠炎症反应与气道重塑的改善作用。【方法】将75只SD大鼠随机分为正常组,模型组,萝卜硫素低、中、高剂量组,每组15只。除正常组外,剩余组采用香烟熏吸结合气管内滴入脂多糖(LPS)法制备COPD模型。建模成功后,连续灌胃给药28 d。给药结束后,观察各组大鼠一般情况,检测肺功能[用力肺活量(FVC)、呼气峰流速(PEF)、1秒用力呼气容积(FEV1)],苏木素-伊红(HE)染色法观察肺组织病理变化,并测量气道重塑指标(支气管壁厚度、平滑肌厚度),酶联免疫吸附分析(ELISA)检测肺组织中炎症因子水平[肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)],蛋白免疫印迹(Western Blot)法检测肺组织Toll样受体4(TLR4)、髓样分化因子88(MyD88)、核转录因子κB(NF-κB)蛋白表达变化。【结果】(1)模型组大鼠毛色干枯且光泽,有明显咳嗽和挠鼻现象,呼吸急促,行动迟缓,喜拱背蜷卧;萝卜硫素低、中、高剂量组大鼠呼吸急促、咳嗽等异常表现明显改善。(2)HE染色显示:模型组大鼠气道壁和平滑肌增厚,气道上皮受损,可见肺泡破坏、融合,炎性细胞大量浸润;萝卜硫素低、中、高剂量组大鼠肺组织病理变化有不同程度的改善,气道壁变薄,肺泡破坏程度减轻,炎性细胞浸润减少。(3)与正常组比较,模型组大鼠FVC、PEF、FEV1显著降低(P<0.05),TNF-α、IL-1β水平,支气管壁厚度、平滑肌厚度,TLR4、MyD88、NF-κB表达水平显著升高(P<0.05);与模型组比较,萝卜硫素低、中、高剂量组大鼠FVC、PEF、FEV1显著升高(P<0.05),TNF-α、IL-1β水平,支气管壁厚度、平滑肌厚度,TLR4、MyD88、NF-κB表达水平显著降低(P<0.05)。【结论】萝卜硫素有助于抑制COPD大鼠炎症反应,减轻大鼠气道重塑,改善大鼠肺组织病理损伤及肺功能,其机制可能与抑制TLR4、MyD88、NF-κB蛋白表达有关。Objective To investigate the ameliorative effect of sulforaphane on inflammatory response and airway remodeling in rats with chronic obstructive pulmonary disease(COPD).Methods Seventy-five SD rats were randomly divided into the normal group,the model group,and the low-,medium-,and high-dose groups of sulforaphane,with 15 rats in each group.Except for the normal group,the COPD model was prepared in the remaining group using aroma smoke inhalation combined with intratracheal droplet lipopolysaccharide(LPS)method.After the successful modelling,the rats were administered the drug by gavage for 28 days.At the end of the administration,the general conditions of the rats in each group were observed,and the lung function[forced vital capacity(FVC),peak expiratory flow-rate(PEF),forceful expiratory volume in 1 second(FEV1)]was examined,and the pathological changes of the lung tissues were observed by hematoxylin-eosin(HE)staining method,and the indexes of airway remodeling(thickness of the bronchial wall,thickness of the smooth muscle)were measured;the enzyme-linked immunosorbent assay(ELISA)was used to examine the lung function of the rats.The levels of inflammatory factors[tumor necrosis factorα(TNF-α),interleukin 1β(IL-1β)]were detected in lung tissue by enzyme-linked immunosorbent assay(ELISA),and changes in the protein expressions of Tolllike receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and nuclear transcription factorκB(NF-κB)were detected in lung tissue by Western Blot.Results(1)The rats in the model group had dry and lack of glossy fur,obvious coughing and nose scratching,shortness of breath,slow movement,and preferred to arch their backs and lie curled up;the rats in the low-,medium-and high-dose groups of sulforaphane showed significant improvement in shortness of breath,coughing,and other abnormal manifestations.(2)HE staining showed that the airway wall and smooth muscle of rats in the model group were thickened,the airway epithelium was damaged,and alveolar destruction,fusion,and massive i

关 键 词：萝卜硫素 慢性阻塞性肺疾病 炎症反应 气道重塑 Toll样受体4(TLR4) 髓样分化因子88(MyD88) 核转录因子κB(NF-κB) 大鼠 

分 类 号：R285.5[医药卫生—中药学]