Cui Di, Xu Jun, Xu Quanyi, Zuo Guokun
Department of Robot and Neuro-Rehabilitation, Ningbo Institute of Industrial Technology, Chinese Academy of Sciences, Ningbo, China; Department of Computer Science, Ningbo University of Technology, Ningbo, China.
Bosn J Basic Med Sci. 2017 Feb 21;17(1):12-16. doi: 10.17305/bjbms.2016.1553.
Cerebral infarction is a type of ischemic stroke and is one of the main causes of irreversible brain damage. Although multiple neuroprotective agents have been investigated recently, the potential of DL-2-amino-3-phosphonopropionic acid (DL-AP3) in treating oxygen-glucose deprivation (OGD)-induced neuronal injury, has not been clarified yet. This study was aimed to explore the role of DL-AP3 in primary neuronal cell cultures. Primary neurons were divided into four groups: (1) a control group that was not treated; (2) DL-AP3 group treated with 10 μM of DL-AP3; (3) OGD group, in which neurons were cultured under OGD conditions; and (4) OGD + DL-AP3 group, in which OGD model was first established and then the cells were treated with 10 μM of DL-AP3. Neuronal viability and apoptosis were measured using Cell Counting Kit-8 and flow cytometry. Expressions of phospho-Akt1 (p-Akt1) and cytochrome c were detected using Western blot. The results showed that DL-AP3 did not affect neuronal viability and apoptosis in DL-AP3 group, nor it changed p-Akt1 and cytochrome c expression (p > 0.05). In OGD + DL-AP3 group, DL-AP3 significantly attenuated the inhibitory effects of OGD on neuronal viability (p < 0.001), and reduced OGD induced apoptosis (p < 0.01). Additionally, the down-regulation of p-Akt1 and up-regulation of cytochrome c, induced by OGD, were recovered to some extent after DL-AP3 treatment (p < 0.05 or p < 0.001). Overall, DL-AP3 could protect primary neurons from OGD-induced injury by affecting the viability and apoptosis of neurons, and by regulating the expressions of p-Akt1 and cytochrome c.
脑梗死是缺血性卒中的一种类型,是不可逆脑损伤的主要原因之一。尽管最近对多种神经保护剂进行了研究,但DL-2-氨基-3-膦丙酸(DL-AP3)治疗氧糖剥夺(OGD)诱导的神经元损伤的潜力尚未明确。本研究旨在探讨DL-AP3在原代神经元细胞培养中的作用。原代神经元分为四组:(1)未处理的对照组;(2)用10μM DL-AP3处理的DL-AP3组;(3)OGD组,其中神经元在OGD条件下培养;(4)OGD + DL-AP3组,其中首先建立OGD模型,然后用10μM DL-AP3处理细胞。使用细胞计数试剂盒-8和流式细胞术测量神经元活力和凋亡。使用蛋白质免疫印迹法检测磷酸化Akt1(p-Akt1)和细胞色素c的表达。结果表明,DL-AP3对DL-AP3组的神经元活力和凋亡没有影响,也没有改变p-Akt1和细胞色素c的表达(p>0.05)。在OGD + DL-AP3组中,DL-AP3显著减轻了OGD对神经元活力的抑制作用(p<0.001),并减少了OGD诱导的凋亡(p<0.01)。此外,OGD诱导的p-Akt1下调和细胞色素c上调在DL-AP3处理后在一定程度上得到恢复(p<0.05或p<0.001)。总体而言,DL-AP3可通过影响神经元的活力和凋亡以及调节p-Akt1和细胞色素c的表达来保护原代神经元免受OGD诱导的损伤。