心肌肥厚及肥厚逆转和慢性心力衰竭大鼠模型的建立及评价体系

Establishment and assessment of pressure-overloaded myocardial hypertrophy, hypertrophy-reverse and chronic heart failure models

目的探讨压力负荷型心肌肥厚（POH）、肥厚逆转和慢性心力衰竭（CHF）大鼠模型的建立及其评价体系。方法8周龄SD雄性大鼠100只编码后按4：1比例分为2组：腹主动脉缩窄（AAC）组（80例）和假手术组（20例），分别行肾上腹主动脉缩窄术或假手术。术后12周，根据超声左心室质量／体质量，AAC组进一步分为心肌肥厚组、肥厚逆转组、心衰组，分别给予正常饮食、福辛普利和卡维地洛灌胃、高盐饮食。结果超声、血流动力学、心质量／体质量、组织形态学等方面证据表明假手术组未发生心肌肥厚和心衰，心肌肥厚组出现明显心肌肥厚，肥厚逆转组表现为心肌肥厚的逆转心衰组则建立了明确的心衰。结论采用AAC法可以建立大鼠POH模型，血管紧张素转换酶抑制剂与B阻滞剂合用可明显恢复POH模型的肥厚心肌而形成肥厚逆转模型，在钠负荷下可促使POH进展为CHF而形成CHF模型。用超声心动图、血流动力学、心肺重量指数、光镜下心肺组织形态学证据结合症状观察，能较好地识别大鼠的心肌肥厚和CHF。

Objective To develop pressure-overloaded myocardial hypertrophy, hypertrophy-reverse and chronic heart failure models and to form an assessing system for the 3 kinds of models. Methods Eight-week-old Sprague-Dawley rats were divided into abdominal aortic eonstrietion（AAC） group and sham group. AAC group was further divided into three groups according to echocardiograph index LVmass/BW at 12 weeks after surgery： myocardial hypertrophy without failure （ POH-NF）, hypertrophy-reverse （POH-Re） and heart failure （POH-F） group, which respectively received normal diet for 4 weeks and were treated with Carvedilol and Fosinopril for 8 weeks and high-salt diet for 12 weeks. Hemodynamic parameters were examined and cardiac contractile function was assessed through eardioeatheter via carotid artery before euthanasia. Hearts and lungs of rats were weighed and part of tissue of hearts and lungs was prepared for histomorphological analysis. Results Compared with sham group, echocardio- graph index end-diastolic ventrieular septal thickness （IVSd）, end-diastolic ventrieular posterior wall thickness （ LVPWd）, left ventrienlar mass （LVmass） of POH-NF group and IVSd, LVPWd, LVmass, left vantricular end-diastolic diameter （LVIDd）, left ventrieular end-systole diameter（LVIDs） of POH-F group increased, whereas frac- tional endocardial shortening（ FS）, ejection fraction（EF） of POH-F group decreased. LVPWd, LVmass of POH-Re group after administration were not significantly different from these of sham group. Basal hemodynamie parameters HR, SBP, left ventrienlar end-systolic pressure （LVESP） and maximum value of the first derivative of the ventrieular pressure wave（dp/dtmax） of POH-NF group increased. SBP, LVESP of POH-Re group recovered. Elevated left ventrieular end-diastolic pressure （LVEDP） and decreased dp/dtmax were found in POH-F group. HW, HW/BW of POH-NF and POH-F group significantly inereased. LW^LW/BW of POH-F group also increased. （ all P 〈0.05）. There were significant myocardial disarray, myocardial hypertrophy and enlarged, strange, densely stained eel nuclear in hearts of POH-NF. Significant lung congestion was found in POH-F group. Conclusion POll model was established by AAC. Angiotension eonverting enzyme inhibitors combined with β-blocker eonld significantly reverse hypertrophic myocardium in POH model to reform a POH-Re model. Meanwhile, it eonld promote POH to chronic heart failure to reform a CHF model. Combination of manifestations, eehocardiography, hemodynamies, weight index of heart, lung and histological observation of heart and lung can set up an assessing system that distinguishes the myocardial hypertrophy in rat CHF models.