Linrong He , Ruolan Lei , Shuangyang Li , Xiaoying Zhao , Xinying He , Xinyue Yang , Ping Liu , Dechou Zhang , Yu Jiang
{"title":"水蛭素通过激活Wnt/β-catenin通路，促进MCAO/R大鼠脑血管生成，发挥神经保护作用。","authors":"Linrong He , Ruolan Lei , Shuangyang Li , Xiaoying Zhao , Xinying He , Xinyue Yang , Ping Liu , Dechou Zhang , Yu Jiang","doi":"10.1016/j.jstrokecerebrovasdis.2024.108218","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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).</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":54368,"journal":{"name":"Journal of Stroke & Cerebrovascular Diseases","volume":"34 3","pages":"Article 108218"},"PeriodicalIF":2.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hirudin promotes cerebral angiogenesis and exerts neuroprotective effects in MCAO/R rats by activating the Wnt/β-catenin pathway\",\"authors\":\"Linrong He , Ruolan Lei , Shuangyang Li , Xiaoying Zhao , Xinying He , Xinyue Yang , Ping Liu , Dechou Zhang , Yu Jiang\",\"doi\":\"10.1016/j.jstrokecerebrovasdis.2024.108218\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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).</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>Hirudin has substantial neuroprotective effects associated with the promotion of angiogenesis in the ischemic penumbra. 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Hirudin promotes cerebral angiogenesis and exerts neuroprotective effects in MCAO/R rats by activating the Wnt/β-catenin pathway
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.
期刊介绍：
The Journal of Stroke & Cerebrovascular Diseases publishes original papers on basic and clinical science related to the fields of stroke and cerebrovascular diseases. The Journal also features review articles, controversies, methods and technical notes, selected case reports and other original articles of special nature. Its editorial mission is to focus on prevention and repair of cerebrovascular disease. Clinical papers emphasize medical and surgical aspects of stroke, clinical trials and design, epidemiology, stroke care delivery systems and outcomes, imaging sciences and rehabilitation of stroke. The Journal will be of special interest to specialists involved in caring for patients with cerebrovascular disease, including neurologists, neurosurgeons and cardiologists.
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