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dl-3-正丁基苯酞对实验性脑出血脑的神经保护作用。

The neuroprotective effect of dl-3-n-butylphthalide on the brain with experimental intracerebral hemorrhage.

机构信息

Department of Neurology, Affiliated Hospital of Yangzhou University, Jiangsu, China.

Department of Pharmacy, Affiliated Hospital of Yangzhou University, Jiangsu, China.

出版信息

Eur J Pharmacol. 2023 Nov 15;959:176105. doi: 10.1016/j.ejphar.2023.176105. Epub 2023 Oct 4.

Abstract

Intracerebral hemorrhage (ICH) is the most devastating subtype of stroke, nevertheless specific treatments with conclusive clinical benefit in improving outcomes of ICH remain lacking. The present study applied dl-3-n-butylphthalide (NBP), a compound approved for the treatment of ischemic stroke and rarely studied in ICH, to an experimental animal model of ICH, aiming to evaluate the therapeutic effects of NBP on ICH and the potential mechanisms. The results showed that rats receiving NBP administration exhibited a structural and functional restoration of brain after ICH mainly manifested as alleviation of neuronal apoptosis, suppression of neuroinflammation and oxidative stress, neurovascular remodeling, and eventually improvement of neurological deficits. In addition, several protein targets of NBP were revealed, which mainly play molecular functions of ribonucleoside triphosphate phosphatase activity, pyrophosphatase activity, hydrolase activity and GTPase activity, and participate in the biological process of brain development by regulating the formation of cellular components such as spindles, polymeric cytoskeletal fibers, microtubules and synapses, through mediating pathways such as VEGF signaling pathway, Fc epsilon RI signaling pathway, ECM-receptor interaction, Fc gamma R-mediated phagocytosis, peroxisome and so on, guiding the mechanism exploration of NBP therapy to some extent. Taken together, the study added some new evidence to the application of NBP in ICH treatment.

摘要

脑出血(ICH)是中风最具破坏性的亚型,但仍缺乏具有明确临床获益的特定治疗方法来改善 ICH 患者的预后。本研究将 dl-3-正丁基苯酞(NBP)应用于 ICH 的实验动物模型,旨在评估 NBP 对 ICH 的治疗作用及其潜在机制。结果表明,ICH 后接受 NBP 治疗的大鼠脑结构和功能得到恢复,主要表现为神经元凋亡减轻、神经炎症和氧化应激抑制、神经血管重塑,最终神经功能缺损改善。此外,还揭示了 NBP 的几个蛋白靶点,它们主要通过调节纺锤体、聚合细胞骨架纤维、微管和突触等细胞成分的形成,发挥核糖核苷酸三磷酸磷酸酶活性、焦磷酸酶活性、水解酶活性和 GTP 酶活性等分子功能,参与脑发育的生物学过程,通过调节 VEGF 信号通路、FcεRI 信号通路、ECM-受体相互作用、FcγR 介导的吞噬作用、过氧化物酶体等途径,为 NBP 治疗的机制探索提供了一些新的证据。总之,该研究为 NBP 在 ICH 治疗中的应用提供了一些新的证据。

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