心脏重构通过大鼠腹主动脉缩窄的模型
Summary
A rat model of abdominal aortic constriction that induces cardiac hypertrophy and remodeling is described. An efficient, highly-reproducible, and minimally-invasive method is used to provide a simple yet useful platform for research in myocardial hypertrophy and dysfunction.
Abstract
Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and fluid retention. Changes in myocardial structure, electrical conduction, and energy metabolism develop with heart failure, leading to contractile dysfunction, increased risk of arrhythmias, and sudden death. Hypertensive heart disease is one of the key contributing factors of cardiac remodeling associated with heart failure. The most commonly-used animal model mimicking hypertensive heart disease is created via surgical interventions, such as by narrowing the aorta. Abdominal aortic constriction is a useful experimental technique to induce a pressure overload, which leads to heart failure. The surgery can be easily performed, without the need for chest opening or mechanical ventilation. Abdominal aortic constriction-induced cardiac pathology progresses gradually, making this model relevant to clinical hypertensive heart failure. Cardiac injury and remodeling can be observed 10 weeks after the surgery. The method described here provides a simple and effective approach to produce a hypertensive heart disease animal model that is suitable for studying disease mechanisms and for testing novel therapeutics.
Introduction
心脏衰竭是一种复杂的临床综合征，其中包括疲劳，呼吸困难症状，运动耐受力，和体液潴留在外围组织。它是死亡的发达国家1的首要原因。除了引起的肌节蛋白质或离子通道2突变遗传性心肌病，心肌功能障碍可以通过各种医学病症，包括高血压，心脏瓣膜疾病，肥胖和糖尿病3引起的。在心肌结构，电传导，和能量代谢导致心脏泵送能力不足的变化，以满足循环的要求，最终导致心脏衰竭3,4。调查心脏衰竭背后的机制，因此，是在心血管领域的研究非常重要。识别导致心脏衰竭恶化的分子机制，最终可以帮助在新的治疗目标的或有用的生物标记物的发现<s达> 1。因此，开发出与人类5心脏衰竭共享关键临床特征心脏衰竭的动物模型非常重要的。
心脏肥大和重塑起着心脏衰竭的发展中起关键作用。高血压心脏疾病是心肌肥厚和人类患者1所示的适应不良重塑的关键因素。模仿这些人类的条件下，动物模型通常通过外科手术成立。特别是，在横向或腹主动脉可以收缩，以增加对左心室，这最终导致在心脏的压力超负荷的阻力。这种现象通常导致心脏肥大，心肌细胞的一生理补偿，以满足对心血管系统的功能需求。然而，功能需求覆盖了正常的生理代偿机制，导致心肌纤维化和承包商瓷砖损害。横向主动脉缩窄（TAC）手术往往涉及复杂的程序，包括开胸，机械通气和胸腺分离和脂肪组织从主动脉弓。相比之下，腹主动脉缩窄，需要简单的实验技术6-8。腹主动脉，在左右肾动脉之间，是在手术过程中收缩。心肌肥厚和重塑可在腹主动脉缩窄手术后6-8可以观察到几个星期;它们产生类似于由横向主动脉缩窄术9,10-生成健壮高血压心脏疾病。在这里，我们描述了一种协议使用高效的，高度可再现的，和微创方法大鼠进行腹主动脉缩窄。邻近肾动脉腹主动脉通过由4-0丝线形成的0.72毫米环收缩。手术，心脏肥大和remodelin十周后g的被观察到。腹主动脉缩窄致心肌肥大的大鼠模型为研究疾病机理与病理生理学，以及潜在疗法的发展平台。
Protocol
Representative Results
Discussion
Hypertensive heart disease, a major health problem that contributes greatly to morbidity and mortality, can lead to cardiac hypertrophy and heart failure5. The pathogenesis and progression of hypertensive heart disease in humans is complex, so an appropriate animal model is critical to investigate the underlying mechanisms and to test novel therapeutics that aim to improve cardiac structure and function5. The abdominal aortic constriction model, which simulates chronic heart disease, is an effective…
Disclosures
The authors have nothing to disclose.
Acknowledgements
The authors’ work was supported by a grant from Ministry of Science and Technology (MOST 103-2320-B-002-068-MY2), the National Health Research Institute (NHRI-EX104-10418SC), and National Taiwan University (NTU 104R4000).
Materials
| 22-Gauge syringe needle | BD Biosciences | 309572 | |
| EDTA Blood Collection Tubes | BD Biosciences | REF365974 | |
| 4-0 silk suture | Sharpoint™ Products | DC-2515N | |
| 6-0 silk suture | Sharpoint™ Products | DC-2150N | |
| Pentobarbital | Sigma Aldrich | 1507002 | |
| Paraformaldehyde | Sigma Aldrich | 441244 | |
| Acetaminophen | Sigma Aldrich | A7085 | |
| Picrosirius red solution | Abcam | ab150681 | |
| Cardiac troponin kit | Abcam | ab200016 | |
| Imagequant | Molecular Dynamics | ||
| Langendorff | ADInstruments | ML870B2 |
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