【作者】 夏峻巍；

【导师】 徐玲；

【作者基本信息】 重庆医科大学 ， 内科学， 2008， 硕士

【摘要】 目的:慢性阻塞性肺疾病(COPD)是一种具有气流受限特征的可预防和治疗的慢性疾病,发病机制复杂,治疗棘手,本研究旨在探讨褪黑素(MLT)对COPD大鼠模型肺部炎症和气道氧化应激的影响,以为其在COPD防治方面提供理论依据。方法: 36只雄性Wistar大鼠随机分成对照组、COPD组、MLT组,采用熏烟加气管注入脂多糖(LPS)复制COPD大鼠模型,MLT组在造模前30min腹腔注入MLT。28d后气管切开测定肺功能,检测肺泡灌洗液(BALF)中白细胞计数及分类, BALF中一氧化氮(NO)、丙二醛(MDA)、总超氧化物歧化酶(T-SOD)、谷光甘肽过氧化物酶(GSH-PX), BALF和肺匀浆的髓过氧化物酶(MPO)、肿瘤坏死因子(TNF-α)、白细胞介素8(IL-8) ,光镜下观察病理形态。结果:⑴MLT组BALF中白细胞总数、中性粒细胞比例较COPD组明显减低(分别为P < 0.01,P < 0.05),单核-巨噬细胞绝对计数下降,均与对照组无显著差异。⑵MLT组大鼠BALF中NO、MDA较COPD组明显减低(P < 0.05), T-SOD、GSH-PX较COPD组明显增高(P < 0.05)。⑶MLT组大鼠BALF和肺匀浆的MPO、TNF-α、IL-8含量均较COPD组显著降低(P < 0.05或P < 0.01)。⑷MLT组0.3s用力呼气容积(FEV0.3)、0.3s用力呼气容积/用力肺活量(FEV0.3/FVC)、峰流速(PEF)较COPD组均有增加,但两者之间无显著性差异(P > 0.05),同时仍较对照组减低(P < 0.05)。⑸COPD组支气管、肺实质病理改变具有特征性,MLT组病理损害减轻,但仍然与对照组有明显差异。结论:对造模成功的COPD动物模型,同予MLT进行干预后大鼠比较发现,后者可以明显减少炎症细胞、炎症介质以及减轻氧化应激、增加抗氧化酶类的活性。提示MLT早期干预能够部分阻止COPD的进程。更多还原

【Abstract】 Objective: Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow limitation that is not fully reversible. The pathogenesis of COPD is complex and it is difficult to treat. To investigate the effect of melatonin (MLT) on lung inflammation and airway oxidative stress in rats with COPD, we could find the theoretical evidence to prevent and manage COPD by MLT.Methods: 36 male wistar rats were randomly divided into 3 groups as follows: control group, COPD group and MLT group. The COPD model was established by intratracheal lipopolysaccharide (LPS) and exposure to cigarette smoking for 28 days, the MLT group was given intraperitoneal injection of 10 mg/kg MLT 30 minutes before each cigarette challenge. After incision of trachea, the lung function was measured. Then the rats were lavaged, the total and different white blood cell counts of bronchial alveolar lavage fluid (BALF) were determined, nitric oxide (NO), malondialdehyde(MDA), total superoxide dismutase(T-SOD), glutathione superoxide (GSH-PX) in BALF were carry out respectively. Then, after the lung homogenates were obtained, we analyzed the content of myeloperoxidase (MPO), tumor necrosis factor (TNF-α), interleukin -8(IL-8) in BALF and homogenates. The pathological changes were observed with light microscope.Results :(1) Significant decrease in total white blood cells and neutrophils in BALF was found in MLT group than these in COPD group (P<0.01, P<0.05, respectively), and the ratio of monocyt-macrophage was lower in MLT group. (2) NO and MDA in BALF of MLT group significantly decreased (P<0.05), T-SOD and GSH-PX in BALF of MLT group significantly increased (P<0.05), compared with those of COPD group. (3)The content of MPO, TNF-α, IL-8 in BALF and lung homogenates of MLT group remarkably decreased compared with those of COPD group (P<0.01 or P<0.05). (4) Forced expiratory volume in 0.3 second (FEV0.3), forced expiratory volume in 0.3 second /forced vital capacity (FEV0.3/FVC) and peak expiratory flow (PEF) in MLT group were higher than those in COPD group, but there were no obvious differences between these groups. (5) The model rats shared specific pathological features in bronchial walls and lung tissues, the pathological damages in MLT group were lessened but still abnormal.Conclusions: We successfully replicated the COPD experimental models .Early intervention with MLT can partly inhibit proceeding of COPD by decreasing the cells and mediators of inflammation, airway oxidative stress and increasing activity of antioxidant.更多还原