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慢性阻塞性肺病大鼠模型的建立及罗布麻干预的影响
Development of an Animal Model for Chronic Obstructive Pulmonary Disease (COPD) and Investigation of Detoxification Effect of Apocynum Venetum
【作者】 林鑫;
【导师】 张小莺;
【作者基本信息】 西北农林科技大学 , 基础兽医, 2012, 硕士
【摘要】 目的:本试验模拟人类机体吸烟及反复呼吸道感染可导致慢性阻塞性肺病(COPD)的过程,采用熏烟加气管注脂多糖LPS法复制大鼠COPD模型,并考察罗布麻对其影响。方法:40只SD大鼠随即分为5组,分别为空白组,模型组,罗布麻高剂量组(800mg/mL),罗布麻中剂量组(400mg/mL),罗布麻低剂量组(200mg/mL)。模型组于第1,10天经气管注入脂多糖0.1mg,熏香烟(第1,10天除外),每天2小时,共20天;试验组于每次熏烟前30分钟灌胃不同剂量的罗布麻提取物。模型建立后,对大鼠进行体征观察;测定血液中碳合血红蛋白(HbCO%)的含量;进行支气管肺泡灌洗,测定支气管肺泡灌洗液(BALF)中细胞数;并对并对肺组织切片行苏木精-伊红(HE)染色观察形态学改变。结果:模型组出现咳嗽、气急、喘息等COPD典型症状;血液分析出现HbCO%显著升高症状;支气管肺泡灌洗液(BALF)中细胞数明显升高;肺组织病理学可见支气管表现出不同程度的慢性炎性细胞浸润,肺泡扩大,肺泡壁断裂。给予罗布麻提取物后,试验组的各项指标均得到改善,且高剂量组优于中低剂量组。结论:熏香烟加气管注脂多糖法可复制较理想的COPD大鼠模型。罗布麻、尤其是高剂量罗布麻,可通过抑制COPD大鼠血液HbCO%的升高,肺部炎性细胞的升高,从而减轻烟毒的危害,延缓COPD的进展。
【Abstract】 Aim: To establish a rat model for chronic obstructive pulmonary disease (COPD) bypassive cigarette smoking plus intratracheal instillation with lipopolysaccharide (LPS), and toinvestigate the protective and therapeutic activities of Apocunum venetum on COPD rats.Methods: Forty SD rats were randomly divided into five groups, including a controlgroup, a model group, and three experimental groups (orally administrated with Apocynumvenetum extract at doses of800mg/mL,400mg/mL and200mg/mL, respectively). The modelgroup was intratracheally instilled with0.1mg lipopolysaccharide (LPS) at Day1and Day10,and the rats were exposed to cigarette smoke for20days for2hours per day (expect for Day1and Day10). Experimental groups were intragastrically administrated with Apocynumvenetum extract of different concentrations (at doses of800mg/mL,400mg/mL and200mg/mL, respectively) for30minutes before exposed to cigarette smoke. After setting upCOPD model, observations of rat signs were conducted; then rat blood samples werecollected, and ratios of carbon monoxide hemoglobin (HbCO) in blood were measured; thebronchoalveolar lavage fluid (BALF) samples were collected, and the total cells in BALFwere counted, and lung tissue slices stained by HE were observed for studying the alternationof morphology.Results: The typical COPD symptoms such as cough and breathing spell were observedin rats from the model group. The percentage of HbCO (HbCO%) in blood collected from themodel group and the total cell counts in BALF collected from the same group weresignificantly higher than the ones of those sampled from the control group. HE stainingshowed that the lung tissues of rats in the model group had typical pathological features ofCOPD and emphysema. The HbCO%in blood and the cell counts in the BALF collected fromexperimental groups administered with Apocynum venetum extract were lower than the onesof those collected from the model group, and HE staining also showed ameliorative symptoms.Furthermore, the protective effect of Apocynum venetum extract of high dose was strongerthan that of medium and low dose groups. Conclusion: A COPD rat model was successfully developed through passive cigarettesmoking plus intratracheal instillation with LPS. Apocynum venetum extracts, especially theone of high dose, had a protective effect on COPD rats by inhibiting the increase of HbCO%in blood and the cell counts in BALF.
【Key words】 chronic obstructive pulmonary disease (COPD); Apocynum venetum; animalmodel; lipopolysaccharide (LPS); rat;