通过激活Rho-酶和神经素1受体,TNF-α引发了血脑屏障功能障碍
1Academic Unit of Mental Health and Clinical Neurosciences, School of Medicine, University of Nottingham, Nottingham, UK.
Immunobiology
|July 16, 2023
概括
这项研究表明,通过向TNF-α通路,抑制Rho激酶或神经素1受体可以在缺血性中风和神经炎症期间保护血脑屏障的完整性.
科学领域:
- 神经科学是一个神经科学.
- 血管生物学 血管生物学
- 细胞生物学 细胞生物学
背景情况:
- 缺血性中风引发神经炎症,损害了血脑屏障 (BBB) 的完整性.
- 这种损伤涉及RhoA/Rho激酶/肌酸酶光链-2和神经素1受体 (NK1R) 途径.
研究的目的:
- 为了研究RhoA/Rho激酶/肌酸酶轻链-2和NK1R在TNF-α诱导的BBB损伤中的作用.
- 评估抑制这些途径的治疗潜力.
主要方法:
- 使用了体外人类BBB模型 (BMEC,星细胞,周细胞).
- 使用TNF-α诱导BBB损伤.
- 通过超内皮电阻和光素流量评估了BBB完整性.
- 抑制了罗基纳酶 (Y-27632) 和NK1R (CP96345).
主要成果:
- TNF-α增加了RhoA活性,Rho激酶和酸化的MLC-2,同时降低了NK1R.
- 抑制Rho激酶或NK1R可以恢复BBB的完整性和功能.
- 这些治疗抑制了RhoA激活,减少了动因应激纤维,并使 zonula occludens-1 局部化正常化.
- Y-27632减弱了TNF-α诱导的NK1R上调,表明RhoA/Rho激酶在NK1R上游起作用.
结论:
- 罗亚/罗亚激酶和NK1R通路是TNF-α诱导BBB破坏的关键调解者.
- 向Rho激酶可以保持内皮细胞形态和屏障功能.
- 对于涉及神经炎症的脑血管疾病,rho 激酶抑制是一种潜在的治疗策略.
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