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脂多糖结合熏烟法和单纯熏烟法建立慢性阻塞性肺病大鼠模型的比较
宋小莲1,2,王昌惠2,白冲1*
0
(1.第二军医大学长海医院呼吸内科,上海 200433;2.同济大学附属第十人民医院呼吸科,上海 200072)
摘要:
目的比较熏香烟加气道内注入脂多糖(LPS)法和单纯熏香烟法建立慢性阻塞性肺病(COPD)大鼠模型的效果。方法8周龄Wistar大鼠24只,随机分为3组,每组8只。其中1组作健康对照,另2组分别进行熏香烟加气道内注入LPS和单纯熏香烟处理建立COPD模型。观察动物一般情况和肺组织病理学,测定肺组织平均内衬间隔 (MLI) 和平均肺泡数 (MAN);检测外周血常规和支气管肺泡灌洗液 (BALF) 常规。结果两个模型组大鼠消瘦,伴有间歇咳嗽和气促,外周血和BALF中的白细胞总数及中性粒细胞百分比均较对照组明显增高(P<0.01);肺组织H-E染色显示两个模型组大鼠均具有慢性支气管炎和肺气肿的典型病变,MLI较对照组明显增高,而MAN较对照组明显下降(P<0.01),但两个模型组组间差异无统计学意义;熏香烟加气道内注入LPS组比单纯熏香烟组气道及肺组织的炎症浸润更明显,单纯熏香烟组主要表现为肺泡过度扩张。结论熏香烟加气道内注入LPS和单纯熏香烟两种方法均可成功制备大鼠COPD模型,其病理生理改变与人类 COPD类似,前者比后者更符合COPD自然发病过程。
关键词:  慢性阻塞性肺疾病  动物模型  炎症  脂多糖  烟草暴露
DOI:10.3724/SP.J.1008.2010.0246
投稿时间:2009-09-27修订日期:2010-02-18
基金项目:国家自然科学基金(30871133).
Establishment of rat chronic obstructive pulmonary disease model: a comparison between exposure to cigarette smoke alone and in combination with intra-tracheal injection of lipopolysaccharide
SONG Xiao-lian1,2, WANG Chang-hui2,BAI Chong1*
(1. Department of Respiratory Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China; 2. Department of Respiratory Diseases, The Tenth People’s Hospital of Shanghai, Tongji University, Shanghai 200072, China)
Abstract:
ObjectiveTo compare the efficacies of exposure to cigarette smoke alone and in combination with intra-tracheal injection of lipopolysaccharide in establishing rat models of chronic obstructive pulmonary disease (COPD). MethodsA total of 24 8-week-old healthy Wistar rats were randomly divided into 2 model groups and a control group (Group C). The rat COPD models were established by two ways: intratracheal injection of lipopolysaccharide (LPS) twice + exposure to cigarette smoke for 1 month (Group A), and cigarette smoke inhalation for 80 days only(Group B). The pathologic characteristics of animal models, including the mean lining interval (MLI) and the mean alveoli number(MAN), were determined. The total and different white blood cell counts in bronchoalveolar lavage fluid(BALF) and blood samples were determined.ResultsThe rats in the two model groups presented with cough or breathlessness periodically, and the white blood cell counts and neutrophil counts in the peripheral blood and BALF were significantly higher than those in the control group (P<0.01). H-E staining showed that the lung tissues of rats in Group A and B had typical pathological features of COPD and emphysema. MLI were significantly higher and MAN were significantly lower in Group A and B than those in group C (both P<0.01), but there was no statistical difference between the two model groups. Group A had more severe inflammatory response in the bronchial and lung tissues than Group B. And Group B was characterized by alveolar overdistension.ConclusionBoth the two methods can successfully establish rat COPD model, with its pathophysiological changes similar to those of human COPD, with intra-tracheal injection of lipopolysaccharide being more consistent to the natural development of disease.
Key words:  chronic obstructive pulmonary disease  animal model  inflammation  lipopolysaccharide  exposure to cigarette smoke