高血糖症通过蛋白质O-GlcNAcylation加剧大脑缺血损伤
Jing Zhu1,2, Xin Ji3,2, Ruirui Shi2
1Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
Journal of Alzheimer's disease : JAD
|June 19, 2023
概括
蛋白质O-GlcNAcylation在高血糖症中恶化缺血性中风损伤,与其在正常情况下的保护作用相反. 阻止这种修饰减轻伤害,建议它作为糖尿病患者中风的治疗目标.
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:
- 阿尔茨海默病 (AD) 患者经常表现出脑血管问题,增加中风风险.
- 高血糖症加剧血管损伤和脑缺血,构成重大威胁.
- 已知蛋白质O-GlcNAcylation可以预防缺血性中风,但其在高血糖引起的恶化中的作用尚不清楚.
研究的目的:
- 研究蛋白质O-GlcNAcylation在高血糖条件下加剧大脑缺血损伤的机制.
- 探索向蛋白质O-GlcNAcylation在与高血糖相关的缺血性中风中的治疗潜力.
主要方法:
- 使用高葡萄糖培养的大脑微血管内皮细胞 (bEnd3) 接受氧气-葡萄糖剥夺.
- 评估中脑动脉封闭后高血糖小鼠的细胞活力,中风结果和出血转变.
- 采用西布洛特来分析亡水平和O-GlcNAcylation调节的影响.
主要成果:
- 在正常的葡萄糖条件下,Thiamet-G抑制O-GlcNAcylation减轻了损伤,但在高葡萄糖条件下则加剧了损伤.
- 在体内,thiamet-g恶化了缺血性损伤和出血性转变,增加了细胞亡.
- 用6-diazo-5-oxo-L-norleucine抑制O-GlcNAcylation可以改善高血糖小鼠的大脑损伤.
结论:
- 蛋白质O-GlcNAcylation在高血糖期间加剧大脑缺血损伤方面发挥着关键作用.
- 向O-GlcNAcylation在高血糖患者,包括患有AD的人中,为缺血性中风提供了潜在的治疗策略.
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