Department of Neurology, Hunan Brain Hospital, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China.
Department of Neurology, The Fourth Hospital of Changsha, Changsha, 410006, Hunan, China.
BMC Neurosci. 2020 May 29;21(1):24. doi: 10.1186/s12868-020-00575-3.
Cerebral stroke occurs following ischemic and hemorrhagic lesions in the brain. Survival and recovery of stroke patients depend on the severity of the initial injury but also the therapeutic approaches applied for emergent lifesaving and continuing post-stroke management. Dl-3-n-Butylphthalide (NBP), an active compound derived from Chinese celery seeds, has shown clinical efficacy in the treatment of ischemic cerebral stroke.
In the present study we explored the therapeutic effect of NBP in a rat model of intracerebral hemorrhage (ICH), focusing on its potential role in promoting neovascularization in the perihemorrhagic zone. ICH was induced in male Sprague-Dawley rats by unilateral injection of autologous blood into the globus pallidus, with sham-operated (Sham group), vehicle-treated (ICH) and NBP-treated (at 10 and 25 mg/kg/Bid, p.o., ICH + NBP10 and ICH + NBP25, respectively) groups examined behaviorally, macroscopically, histologically and biochemically at 1, 3, 7 and 15 days (d) post operation. Rats in the ICH + NBP10 and ICH + NBP25 groups showed reduced Longa's motor scores relative to the ICH groups at the 3 and 7d time points, while the hematoma volume was comparable in the two NBP relative to the ICH groups as measured at 7d and 15d. In the perihemorrhagic zone, the numeric density of blood vessels immunolabeled by CD34, an angiogenic marker, was greater in the ICH + NBP10 and ICH + NBP25 than ICH groups, more so in the higher dosage group, at 1, 3, 7 and 15d. Levels of the vascular endothelial growth factor (VEGF) and angiopoietins-2 (Ang-2) proteins were elevated in the NBP groups relative to the sham and vehicle controls in immunoblotting of tissue lysates from the injection region.
These results suggest that NBP can alleviate neurological defects following experimentally induced local brain hemorrhage, which is associated with a potential role of this drug in promoting neovascularization surrounding the bleeding loci.
脑卒中有缺血性和出血性病变。脑卒中患者的生存和恢复取决于初始损伤的严重程度，但也取决于为挽救生命和继续治疗而应用的治疗方法。N-（3-正丁基）-1-苯丙基-1H-吲唑-5-甲酰胺（NBP）是一种从中国芹菜籽中提取的有效化合物，已显示出在缺血性脑卒中治疗中的临床疗效。
本研究探讨了 NBP 在大鼠脑出血（ICH）模型中的治疗作用，重点研究其在促进出血灶周围新生血管形成中的潜在作用。通过向苍白球内注射自体血诱导雄性 Sprague-Dawley 大鼠 ICH，假手术（Sham 组）、vehicle 处理（ICH 组）和 NBP 处理（10 和 25mg/kg/双日，po，ICH+NBP10 和 ICH+NBP25 组）组在手术后 1、3、7 和 15 天进行行为、宏观、组织学和生化检查。ICH+NBP10 和 ICH+NBP25 组大鼠的 Longa 运动评分相对 ICH 组在 3 和 7 天时间点降低，而在 7 天和 15 天的血肿体积在两个 NBP 组与 ICH 组相比是可比的。在出血灶周围，用 CD34 （一种血管生成标志物）免疫标记的血管数量在 ICH+NBP10 和 ICH+NBP25 组比 ICH 组更多，在高剂量组更多，在 1、3、7 和 15 天。在免疫印迹组织裂解物中，血管内皮生长因子（VEGF）和血管生成素-2（Ang-2）蛋白水平在 NBP 组相对 sham 和 vehicle 对照组升高。
这些结果表明，NBP 可以减轻实验性局部脑出血后神经功能缺陷，这与该药物在促进出血部位周围新生血管形成中的潜在作用有关。
