Accelerated enlargement of experimental abdominal aortic aneurysms in a mouse model of chronic cigarette smoke exposure
Accelerated enlargement of experimental abdominal aortic aneurysms in a mouse model of chronic cigarette smoke exposure
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DOI：
10.1016/j.jamcollsurg.2004.08.010
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发表时间：
2004-12-01
影响因子：
5.2
通讯作者：
Thompson, RW
中科院分区：
文献类型：
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作者：
Buckley, C;Wyble, CW;Thompson, RW
背景：吸烟和肺气肿与腹主动脉瘤(AAAs)密切相关，但与这些疾病相关的生物学机制尚不明确。研究设计：为了确定香烟烟雾暴露是否影响实验性AAAs的形成和生长，129/SvEv小鼠习惯于每日香烟烟雾暴露2周，然后对腹主动脉进行短暂的弹性蛋白酶灌流，以诱导动脉瘤样变性。持续吸烟2周或12周(每组8只)。不吸烟的129名/SvEv对照组(n=29)在相同的时间间隔接受弹性蛋白酶灌注和随访评估。在所有动物中，测量腹主动脉直径(AD)以确定AD的间期增加(DeltaAD)，其中AAAs定义为DeltaAD>；100%。结果：灌流前和灌流后即刻的ADS在实验组之间没有显著差异。吸烟组和非吸烟组小鼠在注射弹性酶2周后均出现动脉瘤扩张，而最终AD组差异无统计学意义(平均+/-扫描电子显微镜：吸烟组1.23+/-0.11 mm，非吸烟组1.22+/-0.05 mm)。在总的主动脉扩张程度(DeltaAD吸烟，136+/-24%与不吸烟，138+/-10%)或AAA发生率(吸烟，75%与不吸烟，79%)方面也没有差异。尽管所有动物在注射弹性酶12周后都出现了AAA，但吸烟小鼠的整体主动脉扩张程度比不吸烟小鼠高50%(DeltaAD吸烟组，204+/-23%，非吸烟组，135+/-17%；p<；0.05)。结论：短期暴露于香烟烟雾中并不改变实验性AAA的初始发展，但长期吸烟暴露与动脉瘤样扩张的晚期进展显著相关。这种体内实验模型的新组合为研究吸烟促进动脉瘤样变性的机制提供了一种新的方法。(C)2004年由美国外科医师学会颁发。
BACKGROUND: Cigarette smoking and pulmonary emphysema are strongly associated with abdominal aortic aneurysms (AAAs), but the biologic mechanisms linking these conditions are undefined.STUDY DESIGN: To determine if exposure to cigarette smoke influences formation and growth of experimental AAAs, 129/SvEv mice were acclimated to daily cigarette smoke exposure for 2 weeks followed by transient elastase perfusion of the abdominal aorta to induce aneurysmal degeneration. Smoking was continued for intervals of either 2 or 12 weeks (8 mice per group). Nonsmoking 129/SvEv controls (n = 29) underwent elastase perfusion and followup evaluation at the same time intervals. In all animals, abdominal aortic diameter (AD) was measured to determine interval increases in AD (DeltaAD), with AAAs defined as a DeltaAD > 100%.RESULTS: Preperfusion and immediate postperfusion ADs were not significantly different between experimental groups. Aneurysmal dilatation was present 2 weeks after elastase perfusion in both smoking mice and nonsmoking controls, with no significant difference in final AD (mean +/- SEM: smoking, 1.23 +/- 0.11 mm versus nonsmoking, 1.22 +/- 0.05 mm). There were also no differences in the overall extent of aortic dilatation (DeltaAD smoking, 136 +/- 24% versus non-smoking, 138 +/- 10%), or the incidence of AAAs (smoking, 75% versus nonsmoking, 79%). Although all animals had developed AAAs by 12 weeks after elastase perfusion, the overall extent of aortic dilatation was 50% greater in smoking mice compared with nonsmoking controls (DeltaAD smoking, 204 +/- 23% versus nonsmoking, 135 +/- 17%; p < 0.05).CONCLUSIONS: Short-term exposure to cigarette smoke did not alter initial development of experimental AAAs, but chronic smoke exposure was associated with a substantial increase in the late progression of aneurysmal dilatation. This novel combination of in vivo experimental models offers a new approach to investigate mechanisms by which cigarette smoking promotes aneurysmal degeneration. (C) 2004 by the American College of Surgeons.