A novel heart failure mice model of hypertensive heart disease by angiotensin II infusion, nephrectomy, and salt loading
A novel heart failure mice model of hypertensive heart disease by angiotensin II infusion, nephrectomy, and salt loading
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DOI：
10.1152/ajpheart.00349.2013
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发表时间：
2013-12-01
影响因子：
4.8
通讯作者：
Komuro, Issei
中科院分区：
文献类型：
--
作者：
Tsukamoto, Yasumasa;Mano, Toshiaki;Komuro, Issei
虽然高血压性心脏病（HHD）的小鼠心力衰竭（HF）模型对于研究HHD的病理生理学和新的治疗靶点是有用的，但是使用简单的实验程序和稳定的表型的模型尚未建立。本研究旨在通过盐负荷和单侧肾切除联合ANG II输注建立一种新的HHD小鼠HF模型。8周龄C57 BL/6雄性小鼠接受ANG II输注（AT）、ANG II输注和单侧肾切除术（AN）、ANG II输注和盐负荷（AS）或ANG II输注、单侧肾切除术和盐负荷（ANS）治疗。AT、AN、AS和ANS小鼠的收缩压显著升高，左心室（LV）肥大，四组之间的这些参数无显著差异。在手术后6周，只有ANS小鼠显示出LV缩短分数的显著降低和肺重量的增加，发生率很高。这种表型是可重复的，并且在实验过程中很少有围手术期或早期死亡。ANS小鼠出现严重的左室纤维化。ANS小鼠心脏中的氧化应激增强，小GTTR Rac 1活性上调。在ANG II输注小鼠模型中加入盐负荷和单侧肾切除术后，心脏功能显著受损，小鼠发生HF。这可能是一个新的和有用的小鼠HF模型，以研究从代偿性左室肥厚的HF在HHD的过渡。
Although the mouse heart failure (HF) model of hypertensive heart disease (HHD) is useful to investigate the pathophysiology and new therapeutic targets for HHD, the model using simple experimental procedures and stable phenotypes has not been established. This study aimed to develop a novel mouse HF model of HHD by combining salt loading and uninephrectomy with ANG II infusion. Eight-week-old C57BL/6 male mice were treated with ANG II infusion (AT), ANG II infusion and uninephrectomy (AN), ANG II infusion and salt loading (AS), or ANG II infusion, uninephrectomy, and salt loading (ANS). Systolic blood pressure was significantly elevated and left ventricular (LV) hypertrophy was found in AT, AN, AS, and ANS mice, and there were no significant differences in those parameters between the four groups. At 6 wk after the procedures, only ANS mice showed significant decreases in LV fractional shortening and increases in lung weight with a high incidence. This phenotype was reproducible, and there were few perioperative or early deaths in the experimental procedures. Severe LV fibrosis was found in ANS mice. Oxidative stress was enhanced and small GTPase Rac1 activity was upregulated in the hearts of ANS mice. After the addition of salt loading and uninephrectomy to the ANG II infusion mouse model, cardiac function was significantly impaired, and mice developed HF. This might be a novel and useful mouse HF model to study the transition from compensated LV hypertrophy to HF in HHD.