聚焦基因治疗的扩张型心肌病模型构建及进展
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甘肃中医药大学

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【基金项目】国家自然科学基金(81860786);甘肃省中医药防治重大疾病科研课题(GZKZD-2018-02);2022年陇原青年创新创业人才项目;白银市科技计划项目(2022-2-50Y);甘肃中医药大学附属医院院内创新基金项目(gzfy-2022-10)


Model construction and progress of focused gene therapy for dilated cardiomyopathy
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甘肃中医药大学

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Funded by Translated by the National Natural Science Foundation of China(81860786);Funded by Scientific Research Project of Traditional Chinese Medicine Prevention and Treatment of Major Diseases in Gansu Province(GZKZD-2018-02);Funded by 2022 Long-yuan Youth Innovation and Entrepreneurship Talent Project;Funded by Bai-yin City Science and Technology Plan Project(2022-2-50Y);Funded by In-hospital Innovation Fund Project of the Affiliated Hospital of Gansu University of Chinese Medicine(gzfy-2022-10)

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    摘要:

    扩张型心肌病是引起心力衰竭的主要疾病之一,存在病因学异质性,近1/4扩张型心肌病患者与遗传相关,心室扩大和心肌收缩功能障碍是该病的主要特征。LMNA突变是遗传性扩张型心肌病的重要病因,心律失常是LMNA突变遗传性扩张型心肌病的重要临床表征。近年来基于C57/B6遗传背景小鼠聚焦基因治疗的啮齿类动物扩张型心肌病模型构建及其干预是研究的热点,以及犬和猪的大动物模型构建也得出了一些重要结论,但关于大动物尤其是非人灵长类依然是更贴近人类的模型,目前对于非人类灵长类动物的心脏疾病模型并未涉及扩张型心肌病,故本文综述了基因层面的扩张型心肌病啮齿类动物及大动物模型的研究,也提出可进行基于当前研究基础上的非人灵长类扩张型心肌病模型的理念,为今后有针对性地研究致病机制以及临床治疗提供新思路。

    Abstract:

    【Abstract】 Dilated cardiomyopathy is one of the main diseases causing heart failure, and there is etiological heterogeneity. Nearly 1/4 of the patients with dilated cardiomyopathy are related to genetics, and ventricular dilation and myocardial systolic dysfunction are the main characteristics of the disease.LMNA mutation is an important cause of hereditary dilated cardiomyopathy, and arrhythmia is an important clinical manifestation of hereditary dilated cardiomyopathy with LMNA mutation.In recent years, the construction and intervention of rodent dilated cardiomyopathy model based on the focused gene therapy of mice with C57/B6 genetic background has been a focus of research, and some important conclusions have been drawn from the construction of large animal models of dogs and pigs. However, large animals, especially non-human primates, are still more close to human models.At present, dilated cardiomyopathy is not involved in the heart disease model of non-human primates. Therefore, this paper reviews the studies on the rodent and large animal models of dilated cardiomyopathy at the genetic level, and also proposes the idea of developing a non-human primate dilated cardiomyopathy model based on the current research.It provides a new idea to study the pathogenesis and clinical treatment in the future.

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  • 收稿日期:2023-05-23
  • 最后修改日期:2023-08-17
  • 录用日期:2023-10-22
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