ラットの腹部大動脈の収縮を通じて心臓リモデリングのモデル
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
心不全は、複雑な臨床症候群、疲労、呼吸困難、運動不耐性を含むそれらの症状、および末梢組織における体液貯留です。これは、先進国1における死亡の主な原因です。別にサルコメアタンパク質またはイオンチャネル2における突然変異によって引き起こされる継承心筋から、心筋機能障害は、高血圧、心臓弁膜症、肥満、および糖尿病3を含む医学的状態、種々の方法により生じさせることができます。最終的には心不全3,4につながる循環要求を満たすために不十分な心臓のポンプ能力、に心筋の構造、電気伝導、およびエネルギー代謝のリードの変化。心不全のメカニズムを調査し、したがって、心臓血管研究の分野において重要です。心不全の進行につながる分子メカニズムを識別することは、最終的に新規治療標的または有用なバイオマーカーの発見を助けることができます<s> 1アップ。ヒト5に心不全とキー臨床的特徴を共有する心不全の動物モデルを開発することが重要です。
心臓肥大及びリモデリングが心不全の発症において重要な役割を果たしています。高血圧性心疾患は、心臓肥大およびヒト患者1に見られる不適応リモデリングの主要な寄与因子です。これらの人間の条件を模倣するために、動物モデルは、多くの場合、外科的処置を介して確立されます。具体的には、横方向または腹部大動脈は、最終的に心臓内の圧負荷につながる左心室に対する抵抗力を高めるために狭窄することができます。この現象は通常、心臓血管系の機能的な要求を満たすために、心臓肥大、心筋細胞の生理学的補償をもたらします。しかし、機能的な需要は、心臓線維症およびcontracにつながる、通常の生理学的代償機構を無効にしますタイルの減損。横方向の大動脈狭窄（TAC）手術は、多くの場合、大動脈弓から開胸、機械換気、および胸腺の分離および脂肪組織を含む複雑な手順を伴います。これとは対照的に、腹部大動脈狭窄は、単純な実験手法6-8を必要とします 。腹部大動脈は、左右の腎動脈との間に、手術中の狭窄です。心肥大およびリモデリングは、数週間腹部大動脈狭窄手術6-8後に観察することができます。彼らは、横大動脈狭窄手術9,10によって生成されたものと同様の堅固な高血圧性心疾患を生じさせます。ここで、我々は、効率的な再現性の高い、かつ低侵襲性の方法を用いて、ラットで腹部大動脈狭窄を行うためのプロトコルを記述します。腎動脈に隣接し、腹部大動脈を4-0絹糸により形成さ0.72ミリメートルループによって絞られます。手術、心臓肥大およびremodelin後10週間gを観察することができます。腹部大動脈狭窄誘発性心肥大のラットモデルは、病気のメカニズムや病態生理学、ならびに潜在的な治療薬の開発を研究するためのプラットフォームを提供します。
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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