基于植入式渗透泵经异丙肾上腺素诱导心肌肥厚模型大鼠条件的改进及评价
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1.中国医学科学院医学实验动物研究所,北京协和医学院比较医学中心,国家卫生健康委员会人类疾病比较医学重点实验室,北京 100021;2.中国医学科学院医学实验动物研究所,北京协和医学院比较医学中心,北京市人类重大疾病实验动物模型工程技术研究中心,北京 100021;3.中国医学科学院医学实验动物研究所,北京协和医学院比较医学中心,国家人类疾病动物模型资源库,北京 100021

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R-33

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Establishment and evaluation of a cardiac hypertrophy rat model induced by ISO administered through a subcutaneously implanted osmotic pump
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1.Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100021, China. 2. Beijing Engineering Research Center for Experimental Animal Models of Human Diseases, Institute of Laboratory Animal Science, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100021. 3. National Human Diseases Animal Model Resource Center, Institute of Laboratory Animal Science, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100021

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    摘要:

    目的 心肌肥厚是一种缓慢发展的有效代偿功能,是对血流动力学或心肌损伤的适应性反应,是导致心衰的独立风险因素。 已有报道显示,经异丙肾上腺素( isoproterenol,ISO)诱导的心肌肥厚大鼠模型,其给药途径和诱导剂量差异很大,模型动物病理表型发展进程不均一。 方法 综合以往方法的先进性、模型表型的均一性、方法稳定性及复制的难易性等因素,本文利用皮下植入渗透泵的方式,采用低剂量长时程给予 ISO(4 mg / kg,持续 28 d)诱导构建心肌肥厚大鼠模型,并利用超声影像、病理组织学染色、免疫荧光染色及 Real-time PCR 等技术对模型表型进行评估。 结果 模型大鼠病理表型典型。 整体表型,包括增大的心脏体积、心室壁厚度及心重指数;细胞表型,包括增大的心肌细胞,严重的心肌纤维化,心肌纤维断裂、溶解,线粒体脊消失、空泡化,心肌 Z 线、M 线以及闰盘扭曲模糊等;分子表型,包括心肌肥厚标志物心钠肽( atrial natriuretic peptide,ANP)及脑钠肽( brain natriuretic peptide,BNP)显著升高。 结论 本文建立的心肌肥厚大鼠模型,方法稳定易复制,表型特征典型,更适于基因功能分析及相关药物筛选等科学研究。

    Abstract:

    Objective Cardiac hypertrophy (CH) is classified into physiologic and pathological types; it can be induced under chronic stress and is an independent risk factor for heart failure. Previous reports have suggested that drug delivery routes and dosage of isoprenaline ( ISO) vary widely. The pathological characteristic of CH animal models varies induced by ISO treatment. Methods We established a rat CH model by subcutaneous implantation of an osmotic pump with low dose of ISO and long duration (4 mg / kg, for 28 days). The phenotypes were determined by echocardiography, histopathological observation, immunofluorescence and Real-time PCR. Results The pathological phenotypes of rats were typical. The overall phenotypes included markedly increased heart size, heart weight to body weight ratio and heart wall thickness. The cell phenotypes included enlarged cardiomyocytes and severe myocardial fibrosis, myocardial fiber rupture and myolysis, mitochondria ridge disappearance and vacuolation, distortion of the Z-line, M-line and leap disk. The molecular phenotypes including increased expression of ANP and BNP. Conclusions The rat model established in this study exhibited typical CH phenotypes. This method is stable and easy to replicate and this model can be used for scientific research such as for gene function analysis and relevant drug screening.

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姜笑雨,刘梦迪,马嘉昕,董 伟,张 旭,张连峰,吕 丹.基于植入式渗透泵经异丙肾上腺素诱导心肌肥厚模型大鼠条件的改进及评价[J].中国比较医学杂志,2022,32(4):60~67.

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  • 收稿日期:2021-02-24
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  • 在线发布日期: 2022-06-20
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自2024年1期开始,杂志参考文献改为中英文对照,具体格式要求可置下载中心查看!
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