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准c-Jun策划了热中风引起的心肌损伤,并揭示了其潜在的生物标志物
Yunfei Xiang1,2,3, Rui Huang2, Xuemei Jiang4
1Department of Traumatology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing, China.
Frontiers in immunology
|November 28, 2025
概括
热中风 (HS) 导致心肌早期损伤,增加死亡率. 这项研究确定c-Jun是诊断和预测HS引起的心脏损伤的关键生物标志物,而ZG-10是潜在的治疗药物.
科学领域:
- 心血管研究研究心血管研究
- 分子生物学分子生物学
- 毒理学 毒理学 毒理学
背景情况:
- 热中风 (HS) 与早期心肌损伤和死亡率增加有关.
- 了解HS引起的心肌损伤的分子机制对于开发有效的治疗方法至关重要.
研究的目的:
- 为了确定关键的基因和途径,涉及热中风引起的心肌损伤.
- 发现新的生物标志物,用于早期诊断和预后HS诱导的心肌损伤.
- 查HS诱导的心肌损伤的潜在治疗药物.
主要方法:
- 权重基因共同表达网络分析 (WGCNA) 和转录组测序被用来识别HS心肌组织中差异表达的基因 (DEG).
- 进行了免疫透,功能丰富和蛋白质-蛋白质相互作用 (PPI) 网络分析.
- 临床验证涉及ELISA和名录构造. 使用L1000FWD平台进行药物查.
- 用HS小鼠和细胞模型来验证治疗疗效.
主要成果:
- 确定了13个候选DEG,与巨细胞,NK细胞和树突细胞相关联.
- 显著丰富了MAPK信号通路. JUN被确定为一个关键的枢纽基因.
- 在HS心肌损伤患者中,c-Jun水平升高显示出诊断准确性 (AUC=0.781). 一个预后性诺图表实现了AUC=0.906.
- 通过抑制JNK/p38 MAPK通路,ZG-10被确定为一种潜在的药物,可以改善心脏功能,并减少HS模型中的炎症和亡.
结论:
- c-Jun在HS引起的心肌损伤中发挥着核心作用,作为诊断和预后的宝贵生物标志物.
- ZG-10代表了HS诱导的心肌损伤的新治疗策略,在临床前模型中证明了有效性.
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