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缺氧诱导因子-1α 在缺血性脑卒中的双面性及其可能相关的途径。

The Janus face of HIF-1α in ischemic stroke and the possible associated pathways.

机构信息

Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China; Department of Zoology, Faculty of Science, Aswan University, Egypt; Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

Institute of Systemic Medicine, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Neurochem Int. 2024 Jul;177:105747. doi: 10.1016/j.neuint.2024.105747. Epub 2024 Apr 22.

Abstract

Stroke is the most devastating disease, causing paralysis and eventually death. Many clinical and experimental trials have been done in search of a new safe and efficient medicine; nevertheless, scientists have yet to discover successful remedies that are also free of adverse effects. This is owing to the variability in intensity, localization, medication routes, and each patient's immune system reaction. HIF-1α represents the modern tool employed to treat stroke diseases due to its functions: downstream genes such as glucose metabolism, angiogenesis, erythropoiesis, and cell survival. Its role can be achieved via two downstream EPO and VEGF strongly related to apoptosis and antioxidant processes. Recently, scientists paid more attention to drugs dealing with the HIF-1 pathway. This review focuses on medicines used for ischemia treatment and their potential HIF-1α pathways. Furthermore, we discussed the interaction between HIF-1α and other biological pathways such as oxidative stress; however, a spotlight has been focused on certain potential signalling contributed to the HIF-1α pathway. HIF-1α is an essential regulator of oxygen balance within cells which affects and controls the expression of thousands of genes related to sustaining homeostasis as oxygen levels fluctuate. HIF-1α's role in ischemic stroke strongly depends on the duration and severity of brain damage after onset. HIF-1α remains difficult to investigate, particularly in ischemic stroke, due to alterations in the acute and chronic phases of the disease, as well as discrepancies between the penumbra and ischemic core. This review emphasizes these contrasts and analyzes the future of this intriguing and demanding field.

摘要

中风是最具破坏性的疾病,可导致瘫痪甚至死亡。为了寻找一种新的安全有效的药物,许多临床和实验研究已经进行,但科学家尚未发现既无不良反应又有效的疗法。这归因于强度、定位、药物途径以及每位患者免疫系统反应的差异。HIF-1α 因其功能成为治疗中风疾病的现代工具:下游基因如葡萄糖代谢、血管生成、红细胞生成和细胞存活。其作用可以通过与细胞凋亡和抗氧化过程密切相关的两个下游 EPO 和 VEGF 来实现。最近,科学家们更加关注针对 HIF-1 途径的药物。本综述重点介绍了用于治疗缺血的药物及其潜在的 HIF-1α 途径。此外,我们讨论了 HIF-1α 与其他生物途径(如氧化应激)之间的相互作用,但特别关注对 HIF-1α 途径有贡献的某些潜在信号。HIF-1α 是细胞内氧平衡的重要调节剂,它影响和控制着与维持体内平衡相关的数千个基因的表达,这些基因与氧水平的波动有关。HIF-1α 在缺血性中风中的作用强烈取决于发病后大脑损伤的持续时间和严重程度。由于疾病的急慢性阶段的变化以及半影区和缺血核心之间的差异,HIF-1α 难以研究,特别是在缺血性中风中。本综述强调了这些对比,并分析了这个引人入胜且具有挑战性的领域的未来。

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