烟熏加气管滴注博莱霉素制备慢性阻塞性肺疾病大鼠模型及白藜芦醇对该疾病的干预作用及机制研究

发布时间：2018-04-04 15:41

  本文选题：博莱霉素　切入点：慢性阻塞性肺疾病　出处：《南京师范大学》2008年硕士论文

【摘要】： 慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是一种以不完全可逆性气流受限为特征的疾病,气流受限逐渐加重,与肺部对有害气体或有害颗粒的异常炎症反应有关。COPD发病率及和病死率较高,严重危害人们的健康。目前COPD的治疗主要是通过药物治疗,松弛气道平滑肌,帮助打开肺部气道,降低气道炎症,减少黏液的产生,改善患者呼吸困难症状和提高生活质量。博莱霉素(BLM)是从轮生链霉菌中提取的一种抗肿瘤药物,它的毒副作用之一是引起肺纤维化,因此实验药理学中可用于肺纤维化造模。白藜芦醇(resveratrol)是一种多酚化合物,体内和体外研究表明白藜芦醇具有抗炎作用,但用于COPD的研究稀有报道。本文用博莱霉素联合烟熏建立新的COPD动物模型,同时探讨白藜芦醇对COPD的干预作用,并探讨其可能的作用机制。 1.博莱霉素联合烟熏建立COPD模型 以单次气管滴注博莱霉素(BLM)及连续27天被动吸烟的方法制作大鼠COPD模型。第29天检测动脉血气参数、肺功能、肺湿/干重比值(W/D),观察肺组织病理学变化,并进行了支气管肺泡灌洗液(BALF)中细胞间粘附分子-1(ICAM-1)含量测定。结果表明该新建大鼠COPD模型组,动脉血氧分压明显降低;肺顺应性(CL)、第0.3秒用力呼气容积(FEV0.3)显著降低;肺W/D值降低,阻塞性肺气肿的特征性病理改变明显;BALF中ICAM-1表达显著增强。结果提示,此大鼠COPD模型肺功能、血气变化及病理学改变均符合COPD的表现,该模型成立。 2.白藜芦醇对COPD的干预作用 由于白藜芦醇难溶于水,实验时以羟丙基-β-环糊精(HP-β-CD)1∶10包合助溶,以生理盐水稀释成所需浓度,每次造模后以4ml·kg~(-1)的剂量雾化吸入。实验第29天,利用肺功能仪测定测定呼吸功能,测肺顺应性(CL)、第0.3秒用力呼气容积(FEV_(0.3))/用力肺活量(FVC)、呼气流量峰值(PEF)、最大呼气中段流量(MMF),收集支气管肺泡灌洗液(BALF),检测其中细胞间粘附分子-1(ICAM-1)含量变化,测定肺W/D值。结果发现白藜芦醇能降低血气Pao_2Δ%、Paco_2Δ%和So_2Δ%,有效改善肺功能,升高FEV_(0.3)/FVC的比值,并降低肺W/D值,光镜下显示肺组织病理学病变均有所改善。 本研究结果表明,博莱霉素及烟熏复合刺激模型比较经典模型,其具有方法可靠、给药剂量可控、制模时间短等优点,利于操作;白藜芦醇减少了ICAM-1的产生,对大鼠COPD具有一定的干预作用,因此,我们推测其作用机制可能与抑制炎症因子的释放有关,对炎症因子释放的抑制可能是白藜芦醇产生保护作用的重要原因。
[Abstract]:Chronic obstructive pulmonary disease (pulmonary) is a disease characterized by incomplete reversible airflow limitation, which is gradually aggravated and is related to the abnormal inflammatory reaction of the lung to harmful gases or particles.It is a serious hazard to people's health.At present, the treatment of COPD is mainly through drug treatment, relaxation of airway smooth muscle, help to open the lung airway, reduce airway inflammation, reduce mucus production, improve the symptoms of dyspnea and improve the quality of life.Bleomycin Bleomycin (BLM) is an antitumor drug extracted from Streptomyces tumefaciens. One of its toxic side effects is pulmonary fibrosis, so it can be used to model pulmonary fibrosis in experimental pharmacology.Resveratrol (resveratrol) is a polyphenol compound. Resveratrol has anti-inflammatory effect in vivo and in vitro.A new animal model of COPD was established with bleomycin combined with fumigation. The intervention of resveratrol on COPD and its possible mechanism were discussed.1.Establishment of COPD Model by Bleomycin combined with fumigationCOPD model of rats was established by single tracheal instillation of bleomycin (BLM) and passive smoking for 27 days.Arterial blood gas parameters, lung function, lung wet / dry weight ratio and lung histopathological changes were observed on the 29th day, and the content of intercellular adhesion molecule-1 (ICAM-1) in bronchoalveolar lavage fluid (BALF) was determined.2.Effect of resveratrol on COPDBecause resveratrol is insoluble in water, HP- 尾 -CD: 1: 10 was used in the experiment, diluted to the required concentration with normal saline, and inhaled with 4ml kg-1 after each modeling.On the 29th day of the experiment, respiratory function was measured by pulmonary function instrument.娴嬭偤椤哄簲鎬，

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