Dissecting aortic aneurysm induced by N-(2-aminoethyl) ethanolamine in rat: Role of defective collagen during development.
Dissecting aortic aneurysm induced by N-(2-aminoethyl) ethanolamine in rat: Role of defective collagen during development.
复制标题
N-(2-氨基乙基)乙醇胺诱导大鼠的解剖主动脉瘤：缺陷型胶原蛋白在发育过程中的作用。
DOI：
10.1002/bdra.23260
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Boor,PaulJ
中科院分区：
文献类型：
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作者：
Xu,Ya;Treumann,Silke;Rossbacher,Roland;Schneider,Steffen;Boor,PaulJ
背景：夹层主动脉瘤（DAA）是主动脉壁上的一个裂口，导致血液在中膜的内侧层之间流动或“剥离”。方法采用工业化学物质n -（2 -氨基乙基）乙醇胺（AEEA）腹腔注射或灌胃处理妊娠大鼠。对新生幼犬的胸主动脉进行了组织学和病理学检查。取AEEA暴露的孕20天胎儿主动脉，进行免疫组化染色和原生Western blot，研究主动脉中1型和3型胶原蛋白的变化。结果AEEA通过腹腔注射或灌胃诱导新生大鼠夹层性主动脉瘤。高剂量灌胃AEEA的DAA发生率可达100%，但与腹腔注射相比无致死性。建立了DAA病变伴AEEA灌胃剂量反应分级系统。免疫组化结果显示妊娠第20天胎鼠主动脉内侧和外膜1型和3型胶原含量降低，分布改变；免疫印迹法证实了这种减少。结论自发性主动脉夹层的体内模型在组织学上与人主动脉夹层具有显著的相似性。因此，该模型可能有助于阐明DAA形成的机制，并探索诊断和治疗策略。AEEA诱导的DAA的发病机制可能与血管壁1型和3型胶原蛋白正常发育过程中的缺陷有关。出生缺陷研究（A部分），2014。©2014 Wiley期刊公司出生缺陷研究（分册）(1):924 - 933,2014。©2014 Wiley期刊公司
BackgroundDissecting aortic aneurysm (DAA) is a tear in the wall of the aorta that causes blood to flow, or “dissect,” between the medial layers of the media.MethodsPregnant rats (dams) were treated with the industrial chemical n‐(2‐aminoethyl) ethanolamine (AEEA) by intraperitoneal injection or gavage. The histology and pathology of aorta in the thorax from newborn pups were examined. Aortas of fetuses of gestational day 20 from dams exposed to AEEA were harvested for immunohistochemical staining and native Western blot to study the changes of collagen type 1 and type 3 in aorta.ResultsDissecting aortic aneurysm of newborn rats was induced by treating with AEEA through intraperitoneal injection or gavage. The incidence of DAA reached 100% in live pups at the high dose by means of gavage of AEEA, but without lethality compared with intraperitoneal injection. A grading system for the dose‐response of DAA lesions associated with AEEA by gavage was established. Gestational day 20 fetuses from treated dams showed a decreased content and altered distribution of medial and adventitial collagen type 1 and 3 in aorta by immunohistochemistry; this decrease was confirmed by native Western blot.ConclusionThis in vivo model of spontaneous aortic dissection bears striking similarities histologically to human aortic dissection. As such, the model conceivably could contribute to elucidating the mechanisms of DAA formation and to exploring diagnostic and therapeutic strategies. The pathogenesis of AEEA‐induced DAA may be related to defects in the normal developmental progression of collagen types 1 and 3 in the vascular wall. Birth Defects Research (Part A), 2014. © 2014 Wiley Periodicals, Inc. Birth Defects Research (Part A) 100:924–933, 2014. © 2014 Wiley Periodicals, Inc.