外源硫化通过通过Nrf2/GPX4信号通路抑制铁亡,缓解与糖尿病相关的认知衰退
Wei Hua1, Yilei Sun2, Mingze Sun2
1Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, PR China.
Life sciences
|January 23, 2026
概括
硫化 (H2S) 治疗通过减少神经元细胞死亡,改善了糖尿病小鼠的认知功能. 这种神经保护通过通过Nrf2/GPX4通路抑制铁亡来实现.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生物化学
- 病理学 病理学 病理学
背景情况:
- 糖尿病相关认知衰退 (DACD) 涉及神经元铁亡.
- 外源硫化 (H2S) 在糖尿病模型中显示出改善认知缺陷的潜力.
研究的目的:
- 为了调查H2S是否通过抑制ferroptosis来保护DACD.
- 确定Nrf2/GPX4信号通路在H2S介导的神经保护中的作用.
主要方法:
- 糖尿病小鼠 (STZ诱导) 用NaHS (H2S供体) 或用Nrf2抑制剂 (ML385) 治疗NaHS.
- 用莫里斯水迷宫测试来评估认知功能.
- 评估了神经元损伤,线粒体形态,氧化应激标志物和蛋白质表达 (Nrf2/GPX4轴).
主要成果:
- H2S治疗改善了认知功能,减少了海马神经元损失,并增强了突触完整性.
- NaHS的使用降低了活性氧物种 (ROS),甲 (MDA) 和铁的含量,同时增加了超氧化溶解酶 (SOD) 和谷氨 (GSH).
- H2S上调了Nrf2/GPX4表达,改善了线粒体功能障碍,并抑制了铁;这些效应被ML385.5逆转了.
结论:
- 外源H2S减轻了与糖尿病相关的认知衰退.
- 通过激活Nrf2/GPX4信号通路,H2S通过抑制铁亡产生神经保护作用.
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