慢性支气管炎、肺气肿并肺动脉高压动物模型的研制  

A rat model of pulmonary hypertension due to chronic bronchitis and emphysema

作　　者：蒋明[1] 钟小宁[1] 柳广南[1] 张建全[1] 

机构地区：[1]广西医科大学第一附属医院呼吸内科

出　　处：《中国呼吸与危重监护杂志》2006年第4期287-291,286,i0001,i0002,共8页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：广西自然科学基金项目资助(桂科自0229024)

摘　　要：目的模拟慢性支气管炎(简称慢支)、肺气肿-肺动脉高压-肺心病的疾病过程,建立慢支、肺气肿并肺动脉高压的实验大鼠模型。方法32只雄性Wistar大鼠随机分成4组(n=8):10%低氧组(A组)、慢支与肺气肿并肺动脉高压组(B组)、18%低氧组(C组)和正常对照组(D组)。A组和C组分别吸入10%、18%低氧8 h/d共2周;B组气管内注入脂多糖(LPS)2次,每天烟熏2 h共6周,后2周叠加18%低氧8 h/d;D组同等条件下无刺激因素饲养6周。各组作血气分析、肺血流动力学测定并对支气管肺泡灌洗液(BALF)行白细胞计数和分类。肺组织HE染色或三联染色后观测气道炎症和肺血管重构的病理改变。免疫组化法检测肺组织中基质金属蛋白酶-2(MMP-2)和MMP-9的表达。结果(1)与D组比较,A组和B组右心室收缩压(RVSP)、平均肺动脉压(mPAP)、右心室与左心室+室间隔重量比(RV/LV+S)显著升高(P<0.05);A组和B组腺泡内肌化型动脉增多、管壁增厚(P<0.05);C组肺血管重构指标无明显改变(P>0.05)。(2)与D组比较,A组白细胞总数无明显差异(P>0.05),B组白细胞总数及中性粒细胞增多(P<0.05)。(3)A组以上皮细胞变性坏死、黏液杯状细胞增生为主,炎细胞浸润不明显;B组气道炎症改变符合慢支、肺气肿改变,气道壁呈现以淋巴细胞为主的多种炎细胞浸润。(4)A组和B组MMP-9和MMP-2阳性表达较D组增强(P<0.05),B组气道、肺血管旁炎细胞MMP-9和MMP-2阳性表达较A组增强(P<0.05)。B组MMP-9阳性表达分布于气道上皮细胞和气道、肺内血管周围浸润的炎症细胞,MMP-2阳性表达主要见于肺内浸润的炎细胞。结论A组和B组病理形态学改变不同,MMPs在两者肺内表达的情况亦有差别。B组同时体现了慢支气道炎症、肺气肿改变和肺血管重构的特征,是模拟人类COPD并肺动脉高压较理想的实验动物模型。Objective To establish a rat model of pulmonary arterial hypertension （PAH） caused by chronic bronchitis （CB） and emphysema. Methods 32 male Wistar rats were randomly divided into 4 groups （ n = 8）. Rats in the group A were exposed to chronic hypoxia （FiO2 = 0.10） 8 hr a day and 6 days in a week for 2 weeks. Rats in the group B were intratracheally instilled of hpopolysaccharide and daily exposed to cigarette smog for 6 weeks and chronic hypoxia （FiO2 = 0.18） 8 hr a day were exposed in last 2 weeks. Rats in the group C were exposed to chronic hypoxia （FiO2 = 0. 18） 8 hr a day for 2 weeks. Rats in the healthy control group were bred for 6 weeks in normal circumstances. The blood gas analysis, pulmonary hemodynamic changes and the morphological changes of airways and pulmonary vascular structure were observed. Total and differential cell counts in bronchoalveocar lavage fluids （BALF） were measured. The expression and enzymatic activity of matrix metalloproteinase-2 （MMP-2） and MMP-9 in lung tissue were detected by immunohistochemistry. Results （1） Compared with group D, right ventricular systolic pressure （RVSP）, mean pulmonary arterial pressure （mPAP） and the ratio of the weight of right ventricle/left ventricle and septum （RV/LV ＋ S） were higher in group A and B.The muscularization of intra-alceolar arteries and the cross-sectional medial vascular wall area of pulmonary arteries were apparent in group A and B （ P 〈 0. 05 ） compared with those in group D. （2） The numbers of total cells and neutrophils in BALF from group B were significantly higher than those in group D （ P 〈 0.05）. （3） Animals in group B showed pathological features in trachea, bronchi and lung tissues similar with COPD. Intensive inflammatory cell, in particular, lymphocytes infiltration was observed in the airways of the group B which was discrete in group A. （4）Immtmoreactivity of MMP-9 was significantly increased in epithelial cells and inflammatory cells,which of MMP-2

关 键 词：慢性支气管炎 肺气肿 肺动脉高压 动物模型 

分 类 号：R-332[医药卫生] R543.2