Guan Junhong, Wei Xiangtai, Qu Shengtao, Lv Tao, Fu Qiang, Yuan Ye
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
Biochem Cell Biol. 2017 Aug;95(4):459-467. doi: 10.1139/bcb-2016-0233. Epub 2017 Mar 3.
Stroke is a common cerebrovascular disease in aging populations, and constitutes the second highest principle cause of mortality and the principle cause of permanent disability, and ischemic stroke is the primary form. Osthole is a coumarin derivative extracted from the fruits of Cnidium monnieri (L.) Cusson. In this study, we established a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo and found that MCAO/R caused cerebral infarction, hippocampus neuronal injury and apoptosis, and also activated the Notch 1 signaling pathway. However, treatment with osthole further enhanced the activity of Notch 1 signaling and reduced the cerebral infarction as well as the hippocampus neuronal injury and apoptosis induced by MCAO/R in a dose-dependent manner. The same results were observed in a primary neuronal oxygen glucose deficiency/reperfusion (OGD/R) model in vitro, and the effect of osthole could be blocked by an inhibitor of Notch 1 signaling, N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine tert-butyl ester (DAPT). Therefore, we demonstrated that osthole injection prevented rat ischemia-reperfusion injury via activating the Notch 1 signaling pathway in vivo and in vitro in a dose-dependent manner, which may be significant for clinical treatment of ischemic stroke.
中风是老年人群中常见的脑血管疾病，是第二大致死原因和永久性残疾的主要原因，缺血性中风是主要形式。蛇床子素是从蛇床果实中提取的一种香豆素衍生物。在本研究中，我们在体内建立了大鼠大脑中动脉闭塞/再灌注（MCAO/R）模型，发现MCAO/R导致脑梗死、海马神经元损伤和凋亡，并激活Notch 1信号通路。然而，蛇床子素治疗进一步增强了Notch 1信号的活性，并以剂量依赖的方式减少了MCAO/R诱导的脑梗死以及海马神经元损伤和凋亡。在体外原代神经元氧糖剥夺/再灌注（OGD/R）模型中也观察到了相同的结果，蛇床子素的作用可被Notch 1信号抑制剂N-[N-(3,5-二氟苯乙酰基)-L-丙氨酰基]-S-苯甘氨酸叔丁酯（DAPT）阻断。因此，我们证明蛇床子素注射通过在体内和体外以剂量依赖的方式激活Notch 1信号通路来预防大鼠缺血再灌注损伤，这可能对缺血性中风的临床治疗具有重要意义。
