丁-3-葡萄糖化物通过向NOX4介导的氧化应激来赋予缺血性中风中的神经保护:一个网络药理学和实验验证研究
Xiaoting Li1, Yikun Gao1, Yingze Ye2
1Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430000, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430000, China.
丁-3-葡萄糖化物 (C-3-G) 通过向NOX4.4来显示对抗缺血性中风的神经保护作用. 这种饮食中所含的安托西亚尼减少了氧化应激和组织损伤,提供了作为辅助疗法的潜力.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 生物化学 生物化学
背景情况:
- 大脑缺血-再输液损伤是中风的重要原因.
- 饮食中含有的反素,如丁-3-葡萄糖化物 (C-3-G),正在研究神经保护性质.
- 了解C-3-G的分子机制对于治疗开发至关重要.
研究的目的:
- 为了研究C-3-G在脑缺血-再输液损伤中的神经保护作用.
- 阐明C-3-G作用的潜在分子机制.
- 确定C-3-G干预的关键治疗目标.
主要方法:
- 采用网络药理学和转录学来确定NOX4作为关键目标.
- 使用in silico方法 (分子对接,布尔网络建模) 验证的发现.
- 实验测试C-3-G在中脑动脉封闭 (MCAO) 的小鼠模型和体外神经元氧气-葡萄糖剥夺/重氧化 (OGD/R) 模型中.
主要成果:
- 网络药理学和PPI分析确定NOX4作为一个中心目标,具有稳定的C-3-G相互作用.
- 转录组学揭示了NOx4上调和氧化应激通路的丰富.
- 在MCAO小鼠中,C-3-G通过抑制Nox4和调节Nrf2-Keap1-HO-1轴,减少了心脏病发作的大小,大脑,并改善了神经功能.
结论:
- 通过向NOX4和调节Nrf2-Keap1-HO-1抗氧化轴,C-3-G可以减轻缺血-再输液损伤.
- C-3-G的神经保护作用主要通过NOX4通路进行介导.
- C-3-G显示出作为急性缺血性中风的辅助治疗的潜力.
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