扩张型心肌病性别差异的机制与精准治疗研究进展
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1南京医科大学第一临床医学院,江苏 南京 211166 ; 2.南京医科大学第一附属医院心血管内科,江苏 南京 210029

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R542.2

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国家自然科学基金(82370322)


Research progress on the mechanisms of gender differences in dilated cardiomyopathy and precision treatment
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1The First School of Clinical Medicine,Nanjing Medical University,Nanjing 211166 ; 2.Department of Cardiology,theFirst Affiliated Hospital of Nanjing Medical University,Nanjing 210029 ,China

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    摘要:

    扩张型心肌病(dilated cardiomyopathy,DCM)存在显著的性别差异,男性发病率约为女性的2~3倍,且往往临床表型更严重、预后更差。作为DCM的相关致病基因,X染色体连锁基因(如DMD,受X染色体失活调控)、Y染色体相关基因(如SRY 和SOX家族)以及部分常染色体基因(如TTN、RBM20、LMNA)在男性中具有更高的外显率或致病性。在分子机制层面,雌激素通过激活雌激素受体(estrogen receptor,ER)α/ERβ及其下游 PI3K/Akt 通路,发挥心脏保护作用;而雄激素则通过雄激素受体(androgen receptor,AR)介导,促进心肌纤维化和不良重构。男性患者还表现出更明显的线粒体功能障碍和更强的慢性炎症反应。基于这些性别相关的分子机制,研究人员提出并开发了一系列“性别精准”诊疗策略,以期为DCM的个体化治疗提供新方向。

    Abstract:

    Dilated cardiomyopathy(DCM)exhibits significant gender differences,the incidence is approximately 2-3 times higher in males than in females,and male patients often present with more severe clinical phenotypes and poorer prognoses. As pathogenic genes related to DCM,X chromosome-linked genes(such as DMD,regulated by X chromosome inactivation),Y chromosome-related genes(such as SRY and SOX families),and some autosomal genes(such as TTN,RBM20,LMNA)have higher penetrance or pathogenicity in males. At the molecular level,estrogen exerts cardioprotective effects mainly through estrogen receptor(ER)α/ERβ- mediated activation of the PI3K/Akt signaling pathway,while testosterone,via androgen receptor(AR)signaling,promotes fibrosis and maladaptive cardiac remodeling. Additionally,male patients tend to exhibit greater mitochondrial dysfunction and heightened inflammatory responses. Based on these gender - related molecular mechanisms,researchers have proposed and developed a series of gender-tailored precision therapies,with the aim of providing new approaches for individualized treatment of DCM.

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印芷睿,崔畅.扩张型心肌病性别差异的机制与精准治疗研究进展[J].南京医科大学学报(自然科学版),2025,45(12):1845-1852

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  • 收稿日期:2025-08-25
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  • 在线发布日期: 2025-12-13
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