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高血糖通过增加过氧化氢的产生加重缺血性脑卒中。

Hyperglycemia exacerbates ischemic stroke not through increased generation of hydrogen peroxide.

机构信息

M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.

Physics Department, International Laser Center, M.V. Lomonosov Moscow State University, Moscow, 119991, Russia.

出版信息

Free Radic Biol Med. 2023 Nov 1;208:153-164. doi: 10.1016/j.freeradbiomed.2023.08.004. Epub 2023 Aug 4.

Abstract

Diabetes is one of the significant risk factors for ischemic stroke. Hyperglycemia exacerbates the pathogenesis of stroke, leading to more extensive cerebral damage and, as a result, to more severe consequences. However, the mechanism whereby the hyperglycemic status in diabetes affects biochemical processes during the development of ischemic injury is still not fully understood. In the present work, we record for the first time the real-time dynamics of HO in the matrix of neuronal mitochondria in vitro in culture and in vivo in the brain tissues of rats during development of ischemic stroke under conditions of hyperglycemia and normal glucose levels. To accomplish this, we used a highly sensitive HyPer7 biosensor and a fiber-optic interface technology. We demonstrated that a high glycemic status does not affect the generation of HO in the tissues of the ischemic core, while significantly exacerbating the consequences of pathogenesis. For the first time using Raman microspectroscopy approach, we have shown how a sharp increase in the blood glucose level increases the relative amount of reduced cytochromes in the mitochondrial electron transport chain in neurons under normal conditions in awake mice.

摘要

糖尿病是缺血性中风的重要危险因素之一。高血糖使中风的发病机制恶化,导致更广泛的脑损伤,从而导致更严重的后果。然而,糖尿病患者的高血糖状态如何影响缺血性损伤发展过程中的生化过程,其机制仍不完全清楚。在本工作中,我们首次记录了在高血糖和正常葡萄糖水平条件下,体外培养的神经元线粒体基质中和体内大鼠脑缺血性中风发展过程中 HO 的实时动力学。为此,我们使用了一种高灵敏度的 HyPer7 生物传感器和光纤接口技术。我们证明,高血糖状态并不影响缺血核心组织中 HO 的产生,而显著加重了发病机制的后果。我们首次使用拉曼微光谱方法表明,在正常情况下,血糖水平急剧升高如何增加清醒小鼠神经元线粒体电子传递链中还原细胞色素的相对含量。

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