Hirudin promotes cerebral angiogenesis and exerts neuroprotective effects in MCAO/R rats by activating the Wnt/-catenin pathway
Research article published in J Stroke Cerebrovasc Dis (2025)
Abstract
OBJECTIVE: Hirudin has shown potential in promoting angiogenesis and providing neuroprotection in ischemic stroke; however, its therapeutic role in promoting cerebrovascular angiogenesis remains unclear. In this study, we aimed to investigate whether hirudin exerts neuroprotective effects by promoting angiogenesis through the regulation of the Wnt/β-catenin signaling pathway. METHODS: An in vitro model of glucose and oxygen deprivation/reperfusion (OGD/R) was established using rat brain microvascular endothelial cells (BMECs). The effects of hirudin on OGD/R cell viability were assessed using the cell counting kit-8 (CCK-8) assay. The angiogenic potential of hirudin was evaluated using Transwell and tube formation assays. In vivo, a middle cerebral artery occlusion/reperfusion (MCAO/R) model was created in rats. The neuroprotective effects of hirudin were assessed using the modified neurological severity score (mNSS), Hematoxylin and eosin (H&E) staining, 2,3,5-Triphenyltetrazolium chloride (TTC) staining, and immunofluorescence staining. Dickkopf-1 (DKK1), a specific inhibitor of this pathway, was introduced in order to investigate the role of the Wnt/β-catenin pathway. The effects of hirudin on the Wnt/β-catenin pathway were examined through immunohistochemistry, western blotting, and reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: Hirudin significantly improved BMEC survival and enhanced both cell migration and tube formation in the OGD/R model. In the MCAO/R model, hirudin reduced the mNSS score, alleviated pathological damage, decreased infarction volume, and increased the expression of key angiogenic factors, including CD34, vascular endothelial growth factor (VEGF), and angiopoietin-2 (Ang-2). In addition, hirudin activated the Wnt/β-catenin pathway, leading to elevated levels of Wnt3a and β-catenin. CONCLUSION: Hirudin has substantial neuroprotective effects associated with the promotion of angiogenesis in the ischemic penumbra. This mechanism is mediated by the regulation of the Wnt/β-catenin pathway.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Резюме
Hirudin has shown potential in promoting angiogenesis and providing neuroprotection in ischemic stroke; however, its therapeutic role in promoting cerebrovascular angiogenesis remains unclear.
Почему это важно для гирудотерапии
В данном исследовании изучалось, оказывает ли гирудин нейропротекторное действие путём стимуляции ангиогенеза через сигнальный путь Wnt/β-катенина, с использованием модели депривации кислорода и глюкозы/реперфузии in vitro на клетках микрососудистого эндотелия головного мозга крыс и модели окклюзии/реперфузии средней мозговой артерии in vivo у крыс. Гирудин улучшил выживаемость клеток эндотелия, их миграцию и тубулообразование in vitro, а in vivo снизил баллы неврологического дефицита, объём инфаркта и патологические повреждения, одновременно увеличив экспрессию ангиогенных факторов (CD34, VEGF, Ang-2) и активировав Wnt3a/β-катенин. Данное исследование релевантно предметной области ASH, поскольку в нём непосредственно изучается гирудин в качестве терапевтического агента при ишемическом инсульте, хотя в реферате не указано его биологическое происхождение или связь с пиявочной терапией. Оговорка: Это доклиническое исследование на животных и in vitro, и его результаты не валидированы в клинических исследованиях на людях.
Цитирование
Hirudin promotes cerebral angiogenesis and exerts neuroprotective effects in MCAO/R rats by activating the Wnt/-catenin pathway.
He L et al. · J Stroke Cerebrovasc Dis, 2025
Связанный клинический контекст
Узнайте, как это исследование связано с клинической практикой
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