Exercise intolerance and systemic manifestations of pulmonary emphysema in a mouse model.
Exercise intolerance and systemic manifestations of pulmonary emphysema in a mouse model.
复制标题
在小鼠模型中锻炼肺肺气肿的耐受性和全身表现。
DOI：
10.1186/1465-9921-10-7
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发表时间：
2009-01-28
影响因子：
5.8
通讯作者：
Andreas S
中科院分区：
文献类型：
--
作者：
Lüthje L;Raupach T;Michels H;Unsöld B;Hasenfuss G;Kögler H;Andreas S
慢性阻塞性肺疾病（COPD）的全身效应对疾病的严重程度和死亡率有显著影响。我们的目标是建立一个慢性阻塞性肺病/肺气肿模型，显示该疾病的全身表现。雌性NMRI小鼠气管内注射猪胰腺弹性酶（肺气肿）或磷酸盐缓冲盐水（对照组）5次。肺气肿的严重程度通过平均线性截距、跑步机跑步距离的运动耐量、分离肌条的膈功能障碍、测量右心室压的肺动脉高压和测定尿去甲肾上腺素浓度的神经体液激活进行组织学量化。肺气肿组的平均线性截距（260.7±26.8 μm）高于对照组（24.7±1.7 μm）。肺气肿小鼠体重减轻，对照组体重增加。肺气肿组的跑步距离比对照组短。与肺气肿组相比，对照组膈肌长度较短。肌条疲劳试验显示肺气肿膈肌松弛受损。与对照组相比，肺气肿组的最大右心室压和去甲肾上腺素升高。跑步距离变化与截距、右心室重量、去甲肾上腺素和横膈膜长度呈线性相关。弹性蛋白酶小鼠模型表现出严重的肺气肿，伴有连续运动限制和神经体液激活。该模型可能加深我们对慢性阻塞性肺病系统性方面的理解。
Systemic effects of chronic obstructive pulmonary disease (COPD) significantly contribute to severity and mortality of the disease. We aimed to develop a COPD/emphysema model exhibiting systemic manifestations of the disease. Female NMRI mice were treated 5 times intratracheally with porcine pancreatic elastase (emphysema) or phosphate-buffered saline (control). Emphysema severity was quantified histologically by mean linear intercept, exercise tolerance by treadmill running distance, diaphragm dysfunction using isolated muscle strips, pulmonary hypertension by measuring right ventricular pressure, and neurohumoral activation by determining urinary norepinephrine concentration. Mean linear intercept was higher in emphysema (260.7 ± 26.8 μm) than in control lungs (24.7 ± 1.7 μm). Emphysema mice lost body weight, controls gained weight. Running distance was shorter in emphysema than in controls. Diaphragm muscle length was shorter in controls compared to emphysema. Fatigue tests of muscle strips revealed impaired relaxation in emphysema diaphragms. Maximum right ventricular pressure and norepinephrine were elevated in emphysema compared to controls. Linear correlations were observed between running distance changes and intercept, right ventricular weight, norepinephrine, and diaphragm length. The elastase mouse model exhibited severe emphysema with consecutive exercise limitation, and neurohumoral activation. The model may deepen our understanding of systemic aspects of COPD.