Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Neurology, School of Medicine, Shanghai Jiao Tong University, Ruijin Hospital, Shanghai, China.
J Cereb Blood Flow Metab. 2019 Oct;39(10):2011-2021. doi: 10.1177/0271678X18776833. Epub 2018 May 15.
Dl-3-N-butylphthalide (NBP) is approved in China for the treatment of ischemic stroke. Previous studies have shown that NBP promotes recovery after stroke via multiple mechanisms. However, the effect of NBP on vascular function and thrombosis remains unclear. Here, we aim to study the effect of NBP on vascular function using a rat model of transient middle cerebral artery occlusion (MCAO) and a state-of-the-art high-resolution synchrotron radiation angiography. Eighty SD rats underwent MCAO surgery. NBP (90 mg/kg) was administrated daily by gavage. Synchrotron radiation angiography was used to evaluate the cerebral vascular perfusion, vasoconstriction, and vasodilation in real-time. Neurological scores, brain infarction and atrophy were evaluated. Real-time PCR was used to assess the expression levels of thrombosis and vasoconstriction-related genes. Results revealed that NBP attenuated thrombosis after MCAO and reduced brain infarct and atrophy volume. NBP administrated at 1 and 4 h after MCAO prevented the vasoconstriction of the artery and maintained its diameter at normal level. Administrated at one week after surgery, NBP functioned as a vasodilator in rats after MCAO while displayed no vasodilating effect in sham group. Our results suggested that NBP attenuates brain injury via increasing the regional blood flow by reducing thrombosis and vasoconstriction.
N-丁基苯酞（NBP）已在中国被批准用于治疗缺血性脑卒中。先前的研究表明，NBP 通过多种机制促进脑卒中后的恢复。然而，NBP 对血管功能和血栓形成的影响仍不清楚。在这里，我们旨在使用短暂性大脑中动脉闭塞（MCAO）大鼠模型和最先进的高分辨率同步辐射血管造影术来研究 NBP 对血管功能的影响。80 只 SD 大鼠接受 MCAO 手术。NBP（90mg/kg）每日通过灌胃给药。同步辐射血管造影术用于实时评估脑血管灌注、血管收缩和血管扩张。评估神经功能评分、脑梗死和萎缩情况。实时 PCR 用于评估血栓形成和血管收缩相关基因的表达水平。结果表明，NBP 减轻了 MCAO 后的血栓形成，减少了脑梗死和萎缩体积。MCAO 后 1 小时和 4 小时给予 NBP 可防止动脉收缩，并保持其正常直径。手术后一周给予 NBP，可作为 MCAO 大鼠的血管扩张剂，而在假手术组中无血管扩张作用。我们的结果表明，NBP 通过减少血栓形成和血管收缩来增加局部血流量，从而减轻脑损伤。
