内皮细胞流量介导创伤诱导的内皮透气性
Terry R Schaid1, Sanchayita Mitra1, Preston Stafford1
1Department of Surgery, Trauma Research Center, School of Medicine, University of Colorado Denver, Aurora, CO.
Annals of surgery
|December 11, 2023
概括
创伤患者的血会通过TRPV4通道引起内皮的流入,从而增加透性. 抑制TRPV4可以降低这种效果,为内皮皮质病提供潜在的治疗点.
科学领域:
- 创伤研究研究创伤研究
- 内皮细胞生物学 内皮细胞生物学
- 信号传递的.
背景情况:
- 内皮透性是创伤后器官功能障碍的一个关键因素.
- 驱动这种增加透性的精确机制仍然不完全理解.
- 新出现的证据表明,细胞内 (Ca2+) 信号通路可能发挥作用.
研究的目的:
- 为了确定受伤患者的血是否诱导内皮Ca2+流入.
- 调查Ca 2+流入作为创伤诱导的内皮膜透性的机制.
- 探索TRPV4频道在这个过程中的作用.
主要方法:
- 用创伤患者的ex vivo血治疗内皮细胞 (根据受伤/冲击严重程度分类).
- 对细胞外Ca2+水平和细胞内Ca2+储量的实验性操纵.
- 药理上抑制了短暂受体潜在化物4 (TRPV4) 通道.
- 使用显微镜和阻抗传感评估细胞质Ca 2+水平,内皮透性和细胞骨变化.
主要成果:
- 从严重受伤/震惊的患者的血诱导显著更大的细胞溶液Ca 2+增加相比较不严重受伤的患者.
- 内皮Ca 2+的流入和随后的透性取决于细胞外Ca 2+.
- 抑制TRPV4通道减少创伤等离子体诱导的Ca2+流入和内皮透性.
结论:
- 创伤后内皮质变性病的新机制涉及通过TRPV4通道的Ca2+流入.
- 抑制TRPV4显示出减轻创伤诱导的内皮透气性的潜力.
- 研究结果表明,内皮Ca2+流入和创伤引起的低血症之间存在机械联系,为Ca2+向治疗铺平了道路.
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