Department of Pharmacy, The People's Hospital of Yichun City, Yichun, 336000, People's Republic of China.
Department of Neurology, The People's Hospital of Yichun City, Yichun, 336000, People's Republic of China.
Exp Brain Res. 2021 Jan;239(1):341-350. doi: 10.1007/s00221-020-05978-6. Epub 2020 Nov 12.
Cerebral ischemia/reperfusion (I/R) injury may lead to a poor prognosis for ischemic stroke patients after reperfusion therapy, and currently, lacks effective therapeutic intervention. This study aimed to investigate the effects of L-3-n-butylphthalide (L-NBP) on cerebral I/R injury in rats. Rat models of cerebral I/R injury were established using the middle cerebral artery occlusion/refusion (MACO/R) surgery and were administrated intragastrically with L-NBP or vehicle. We found that L-NBP attenuated the histological damages and reduced the brain hematoma in MACO/R rats. L-NBP also significantly improved the neurological function, alleviated the brain edema, and reduced the permeability of blood-brain barrier of MACO/R rats. Moreover, we detected that L-NBP considerably facilitated microvessel formation in the lesion area of brain in MACO/R rats. Finally, we found that L-NBP significantly increased the protein and mRNA expression levels of Nrf2, HIF-1α, and VEGF in the brain of MACO/R rats. In conclusion, our results demonstrated that L-NBP exerted significant beneficial effects on cerebral I/R injury in rats through promoting angiogenesis, which may be associated with the activation of Nrf2/HIF-1α/VEGF signaling pathway. Our results suggested that L-NBP could be a potential therapeutic drug for cerebral I/R injury.
脑缺血/再灌注(I/R)损伤可能导致缺血性脑卒中患者再灌注治疗后的预后不良,目前缺乏有效的治疗干预措施。本研究旨在探讨 L-3-正丁基苯酞(L-NBP)对大鼠脑 I/R 损伤的影响。采用大脑中动脉闭塞/再灌注(MACO/R)手术建立大鼠脑 I/R 损伤模型,并给予 L-NBP 或载体灌胃。结果发现,L-NBP 可减轻 MACO/R 大鼠的组织损伤和脑血肿。L-NBP 还显著改善了 MACO/R 大鼠的神经功能,减轻了脑水肿,降低了血脑屏障的通透性。此外,我们检测到 L-NBP 可显著促进 MACO/R 大鼠损伤区域的微血管形成。最后,我们发现 L-NBP 可显著增加 MACO/R 大鼠脑组织中 Nrf2、HIF-1α 和 VEGF 的蛋白和 mRNA 表达水平。综上所述,我们的研究结果表明,L-NBP 通过促进血管生成对大鼠脑 I/R 损伤发挥显著的有益作用,这可能与 Nrf2/HIF-1α/VEGF 信号通路的激活有关。这些结果表明,L-NBP 可能是一种治疗脑 I/R 损伤的潜在药物。