用伊马替尼布有效治疗水和内皮屏障功能障碍
Jurjan Aman1, Jan van Bezu, Amin Damanafshan
1Department of Physiology, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.
伊马替尼有效地通过抑制Abl相关基因激酶 (Arg) 来治疗,这是治疗血管透性和相关疾病的新目标.
科学领域:
- 生物医学研究生物医学研究
- 分子生物学分子生物学
- 血管生物学 血管生物学
背景情况:
- 组织和内皮屏障功能障碍在败血症和急性肺损伤中至关重要,缺乏向治疗.
- 之前的一份病例报告表明,伊马替尼 (一种激酶激素抑制剂) 通过不清楚的机制快速解决肺.
- 这项研究研究了伊马替尼对内皮屏障功能障碍和水形成的精确影响.
研究的目的:
- 阐明伊马替尼 (imatinib) 影响内皮屏障功能的机制.
- 为了确定伊马替尼在调节内皮透气性方面所涉及的特定分子标.
- 在和血管泄漏模型中评估伊马替尼的治疗潜力.
主要方法:
- 在体外研究中,使用暴露于血栓激素和胰岛素的人体内皮细胞单层.
- 在体内实验中,利用对血管泄漏和败血症的小鼠模型进行实验.
- 利用小干扰RNA (siRNA) 来击败对伊马替尼布敏感的激酶,包括与Abl相关的基因激酶 (Arg/Abl2).
主要成果:
- 伊马替尼减弱的内皮屏障功能障碍因体内血栓素和组胺而引起.
- 与ABL相关的基因激酶 (Arg/Abl2) 被确定为内皮屏障功能障碍的关键媒介,由血栓素,组胺和VEGF激活.
- 伊马替尼通过增强Rac1活性和内皮细胞粘附来限制Arg介导功能障碍;它减少了小鼠模型中的血管泄漏和败血症模型中的.
结论:
- 伊马蒂尼布通过抑制Arg.防止内皮屏障功能障碍和水通过抑制Arg.
- 这些发现突出了Arg作为瘤的新治疗标.
- 伊马替尼 (imatinib) 是一种有前途的透性的治疗方法.
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