心肌纤维化研究进展
Progress in research on myocardial fibrosis
熊由俊 1周序锋 2黄鈺婷 2胡硕 2李佩俊 2田承南2
作者信息
- 1. 赣南医科大学第一临床医学院
- 2. 赣南医科大学第一附属医院,江西 赣州 341000
- 折叠
摘要
心肌纤维化是大多数心脏疾病常见的病理生理改变,常伴有收缩、舒张功能障碍以及心律失常等导致不良预后,心肌纤维化既是心力衰竭治疗的直接靶点和间接靶点,是心力衰竭发展和进展的关键因素,在心力衰竭发展过程中具有预后价值.尽管已有大量研究探索相关治疗靶点,临床治疗仍偏重于后期干预,缺乏有效的动物模型来研究人类心肌纤维化的病理过程.本文综述了心肌纤维化的病理生理、心肌纤维化的相关分子机制及心肌纤维化相关动物模型研究.心肌纤维化有替代性纤维化和反应性纤维化2种类型,主要由活化的成纤维细胞(肌成纤维细胞)驱动,伴胶原蛋白合成增加.多种分子机制参与心肌纤维化的发生,如基质金属蛋白酶(Matrix metalloproteinases,MMPs)、转化生长因子β(Transforming growth factor-β,TGF-β)、结缔组织生长因子(Connective tissue growth factor,CTGF)、血小板衍生生长因子(Platelet-derived growth factor,PDGF)、活性氧(Reactive oxygen species,ROS)等.此外,微小RNA(microRNAs,miRNAs)和肾素-血管紧张素-醛固酮系统(Renin-angiotensin-aldosterone system,RAAS)也在心肌纤维化中发挥重要作用.在动物模型方面,心肌纤维化的研究主要集中于小鼠和大动物模型,小鼠模型用于基因机制研究,大动物模型则更接近人类的生理特征.未来的研究应关注开发更符合人类生理状态的大动物模型,以便更好地理解心肌纤维化的机制并寻找新的治疗靶点.
Abstract
Myocardial fibrosis is a common pathophysiological change in most cardiac diseases,often accompanied by systolic,diastolic dysfunction and arrhythmia,leading to poor prognosis.Myocardial fibrosis serves as both a direct and indirect target for heart failure treatment and is a critical factor in the development and progression of heart failure,possessing prognostic value throughout this process.Despite numerous studies exploring related therapeutic targets,clinical treatment still tends to focus on late-stage interventions,and there is a lack of effective animal models for studying the pathological processes of human myocardial fibrosis.This article reviews the pathophysiology of myocardial fibrosis,its associated molecular mechanisms,and research on animal models related to myocardial fibrosis.Myocardial fibrosis involves the abnormal accumulation of the extracellular matrix(ECM),which can be categorized into two types:replacement fibrosis and reactive fibrosis.It is primarily driven by activated fibroblasts(myofibroblasts),accompanied by increased collagen synthesis.Several molecular mechanisms are implicated in the development of myocardial fibrosis,including matrix metalloproteinases(MMPs),transforming growth factor-β(TGF-β),connective tissue growth factor(CTGF),platelet-derived growth factor(PDGF),and reactive oxygen species(ROS).Additionally,microRNAs(miRNAs)and the renin-angiotensin-aldosterone system(RAAS)also play significant roles in myocardial fibrosis.In terms of animal models,research on myocardial fibrosis primarily focuses on both mouse and large animal models.The former is utilized for genetic mechanism studies,while the latter is more closely aligned with human physiological characteristics.Future research should emphasize the development of large animal models that more accurately reflect human physiological states to better understand the mechanisms of myocardial fibrosis and identify new therapeutic targets.
关键词
心肌纤维化/分子机制/动物模型Key words
Myocardial fibrosis/Molecular mechanisms/Animal models引用本文复制引用
出版年
2024
国家科技期刊平台
NSTL
万方数据