本文選題：博萊霉素　切入點：慢性阻塞性肺疾病　出處：《南京師范大學》2008年碩士論文

【摘要】： 慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是一種以不完全可逆性氣流受限為特征的疾病,氣流受限逐漸加重,與肺部對有害氣體或有害顆粒的異常炎癥反應有關(guān)。COPD發(fā)病率及和病死率較高,嚴重危害人們的健康。目前COPD的治療主要是通過藥物治療,松弛氣道平滑肌,幫助打開肺部氣道,降低氣道炎癥,減少黏液的產(chǎn)生,改善患者呼吸困難癥狀和提高生活質(zhì)量。博萊霉素(BLM)是從輪生鏈霉菌中提取的一種抗腫瘤藥物,它的毒副作用之一是引起肺纖維化,因此實驗藥理學中可用于肺纖維化造模。白藜蘆醇(resveratrol)是一種多酚化合物,體內(nèi)和體外研究表明白藜蘆醇具有抗炎作用,但用于COPD的研究稀有報道。本文用博萊霉素聯(lián)合煙熏建立新的COPD動物模型,同時探討白藜蘆醇對COPD的干預作用,并探討其可能的作用機制。 1.博萊霉素聯(lián)合煙熏建立COPD模型 以單次氣管滴注博萊霉素(BLM)及連續(xù)27天被動吸煙的方法制作大鼠COPD模型。第29天檢測動脈血氣參數(shù)、肺功能、肺濕/干重比值(W/D),觀察肺組織病理學變化,并進行了支氣管肺泡灌洗液(BALF)中細胞間粘附分子-1(ICAM-1)含量測定。結(jié)果表明該新建大鼠COPD模型組,動脈血氧分壓明顯降低;肺順應性(CL)、第0.3秒用力呼氣容積(FEV0.3)顯著降低;肺W/D值降低,阻塞性肺氣腫的特征性病理改變明顯;BALF中ICAM-1表達顯著增強。結(jié)果提示,此大鼠COPD模型肺功能、血氣變化及病理學改變均符合COPD的表現(xiàn),該模型成立。 2.白藜蘆醇對COPD的干預作用 由于白藜蘆醇難溶于水,實驗時以羥丙基-β-環(huán)糊精(HP-β-CD)1∶10包合助溶,以生理鹽水稀釋成所需濃度,每次造模后以4ml·kg~(-1)的劑量霧化吸入。實驗第29天,利用肺功能儀測定測定呼吸功能,測肺順應性(CL)、第0.3秒用力呼氣容積(FEV_(0.3))/用力肺活量(FVC)、呼氣流量峰值(PEF)、最大呼氣中段流量(MMF),收集支氣管肺泡灌洗液(BALF),檢測其中細胞間粘附分子-1(ICAM-1)含量變化,測定肺W/D值。結(jié)果發(fā)現(xiàn)白藜蘆醇能降低血氣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,光鏡下顯示肺組織病理學病變均有所改善。 本研究結(jié)果表明,博萊霉素及煙熏復合刺激模型比較經(jīng)典模型,其具有方法可靠、給藥劑量可控、制模時間短等優(yōu)點,利于操作;白藜蘆醇減少了ICAM-1的產(chǎn)生,對大鼠COPD具有一定的干預作用,因此,我們推測其作用機制可能與抑制炎癥因子的釋放有關(guān),對炎癥因子釋放的抑制可能是白藜蘆醇產(chǎn)生保護作用的重要原因。
[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.嫻嬭偤欏哄簲鎬，

本文編號：1710606