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Updated: Feb 3, 2026

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Porcine Model of Infrarenal Abdominal Aortic Aneurysm
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CD95联体驱动腹腔大动脉瘤通过Caspase-8介导的GSDMD-依赖性内皮质质灭症的进展:由SRC激酶调节
Tian-Tian Ke1, Chuan Yuan2, Yong Yuan3
1Department of Anesthesiology and Operation, Medical Center of Anesthesiology and Pain, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People's Republic of China.
Apoptosis : an international journal on programmed cell death
|February 1, 2026
概括
CD95连接体 (CD95L) 通过激活Caspase-8在腹腔大动脉动脉瘤 (AAA) 中触发了称为 pyroptosis的编程细胞死亡. 抑制Caspase-8或激活SRC激酶可以治疗AAA.
科学领域:
- 血管生物学 血管生物学
- 免疫学 免疫学 免疫学
- 细胞死亡机制 细胞死亡机制
背景情况:
- 腹腔大动脉瘤 (AAA) 的进展包括炎症和内皮功能障碍.
- 以前的研究通过调节炎症来将CD95连接体 (CD95L) 和Caspase-8与AAA病变发生联系起来.
- CD95L/Caspase-8信号加剧AAA相关炎症的确切机制尚不清楚.
研究的目的:
- 为了研究CD95L/Caspase-8信号如何驱动AAA中的内皮质质.
- 阐明将CD95L/Caspase-8与热和AAA进展联系起来的分子机制.
- 通过调节该途径来评估AAA的潜在治疗点.
主要方法:
- 使用了CaCl2诱导的AAA小鼠模型和小鼠主动脉内皮细胞 (MAECs).
- 评估了内皮皮质灭标志物,包括NLRP3炎症酶激活,Gasdermin D N-终端 (GSDMD-N) 裂变和Caspase-8/Caspase 1激活.
- 采用电子显微镜,流细胞计,siRNA,特定抑制剂 (Z-IETD-FMK),AAV9-shRNA用于Caspase-8敲击,并评估了SRC激酶活性.
主要成果:
- 在MAEC和AAA小鼠模型中,CD95L诱导了内皮质质炎,通过形态学和特定的分子标记物得到证实.
- CD95L抑制了Caspase-8酸化,导致其激活和随后的GSDMD-依赖性热亡.
- 特定于内皮细胞的Caspase-8 Knockdown和SRC激酶激活减弱了AAA进展,减少了热致死标志物,并保持了血管完整性.
- 作为对CD95L的反应,IL-1β和IL-18分泌量的增加取决于Caspase-8的激活.
结论:
- 在AAA中,CD95L是通过Caspase-8脱和NLRP3/GSDMD-N通路的激活来促进内皮质灭的关键调解者.
- 向Caspase-8或增强SRC激酶活性提供了一个有前途的治疗策略来抑制AAA进展.
- 通过调节CD95L/Caspase-8信号传导来保持内皮静止对于管理AAA至关重要.
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