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鼻内胰岛素的使用通过调节运输蛋白质复合物IP3R/GRP75/VDAC1在MAM上影响外科手术期间的神经认知功能障碍
Huiqin Liu1, Yanhua Jiang1, Lianhui Cong1
1Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, China.
Free radical biology & medicine
|January 6, 2025
概括
鼻内胰岛素通过改善线粒体功能和保护神经元来预防手术后的认知衰退. 这为患有术前神经认知障碍 (PND) 风险的老年患者提供了潜在的新疗法.
科学领域:
- 神经科学是一个神经科学.
- 线粒体生物学 线粒体生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 手术前神经认知障碍 (PND) 在手术后很常见,特别是在老年人中.
- PND与神经元能量代谢受损和线粒体功能障碍有关.
- 向与线粒体相关的内质网膜 (MAMs) 可能提供一种治疗途径.
研究的目的:
- 调查鼻内胰岛素作为预防PND的策略.
- 研究IP3R/GRP75/VDAC1复合体在PND中的作用.
- 评估胰岛素对神经元功能和线粒体健康的影响.
主要方法:
- 在小鼠中进行部分肝切除术以诱导PND,随后进行鼻内胰岛素或盐水治疗.
- 通过莫里斯水迷宫评估认知功能;分析海马体组织的蛋白质表达和亡.
- 用于模拟外科创伤的体外细胞共同培养;IP3R敲击评估.
主要成果:
- 鼻内胰岛素改善了小鼠的认知功能,并减少了神经元亡.
- 胰岛素调节了IP3R/GRP75/VDAC1复合体,促进了线粒体ATP的产生,并稳定了MAMs.
- 胰岛素激活PI3K/AKT信号传递,而IP3R倒置在体外减少了氧化应激和亡.
结论:
- 鼻内胰岛素通过向IP3R/GRP75/VDAC1复合体和通过PI3K/AKT通路增强线粒体功能来减轻PND.
- 这种方法对在手术患者中预防和管理PND有希望.
- 鼻内胰岛素可以改善手术结果,特别是在老年人群中.
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