高盐环境下醋酸脱氧皮质酮或醛固酮致小鼠主动脉瘤模型的建立

M. Gong, Shu Liu, Zhenheng Guo
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摘要

肾素-血管紧张素-醛固酮系统(RAAS)与许多心血管疾病的病因有关,包括腹主动脉瘤(AAA)和胸主动脉瘤(TAA)。特别是在高脂血症小鼠中输注血管紧张素II (Ang II)诱导AAA和TAA已被广泛应用于该领域,提示Ang II在主动脉瘤中的关键作用。相比之下,醛固酮(Aldo)作为Ang II的下游效应物是否参与主动脉瘤尚不清楚。本研究建立了高盐环境下10月龄C57BL/6雄性小鼠皮下植入醋酸去氧皮质酮(DOCA)微丸或渗透泵灌注Aldo诱导的AAA和TAA小鼠模型。DOCA或aldo -salt诱导的主动脉瘤依赖于矿物皮质激素受体的激活,但不依赖于Ang II和高血压,并表现出模仿人主动脉瘤的几个独特特征。本文综述了目前国际上常见的AAA、TAA和主动脉夹层动物模型,重点介绍了DOCA-或Aldo-salt小鼠主动脉瘤模型。DOCA-或Aldo-salt小鼠主动脉瘤模型对当前AAA病因、临床诊断、评价和治疗的基础研究和临床实践的意义及潜在影响。
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A New Mouse Model of Aortic Aneurysm Induced by Deoxycorticosterone Acetate or Aldosterone in the Presence of High Salt
The renin-angiotensin-aldosterone system (RAAS) is implicated in the etiologies of many cardiovascular diseases, including abdominal aortic aneurysm (AAA) and thoracic aortic aneurysm (TAA). In particular, the infusion of angiotensin II (Ang II) in hyperlipidemia mice to induce AAA and TAA has been extensively used in the field, suggesting a critical role of Ang II in aortic aneurysm. In contrast, whether aldosterone (Aldo), a downstream effector of Ang II, is involved in aortic aneurysm is unknown. Here, we describe a new mouse model of AAA and TAA induced by subcutaneous implantation of deoxycorticosterone acetate (DOCA) pellets or infusion of Aldo using osmotic pumps to 10-month-old C57BL/6 male mice in the presence of high salt. The DOCA- or Aldo-salt-induced aortic aneurysm is dependent upon mineralocorticoid receptor activation but independent of Ang II and hypertension and exhibits several unique features that mimic human aortic aneurysm. This review aims to discuss the common animal models of AAA, TAA, and aortic dissection currently studied in the world with the most focus on the DOCA- or Aldo-salt mouse model of aortic aneurysm. significance and potential impact of the DOCA- or Aldo-salt mouse model of aortic aneurysm on the current basic research and clinical practice on the etiology, clinic diagnosis, evaluation, and treatment of AAA.
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