Wang Shu-Na, Xu Tian-Ying, Wang Xia, Guan Yun-Feng, Zhang Sai-Long, Wang Pei, Miao Chao-Yu
Department of Pharmacology, Second Military Medical University, Shanghai, China.
Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China.
CNS Neurosci Ther. 2016 Sep;22(9):782-8. doi: 10.1111/cns.12576. Epub 2016 Jun 23.
NAMPT is a novel therapeutic target of ischemic stroke. The aim of this study was to investigate the effect of a potential NAMPT activator, P7C3-A20, an aminopropyl carbazole derivative, on ischemic stroke.
In vitro study, neuron protection effect of P7C3-A20 was investigated by co-incubation with primary neurons subjected to oxygen-glucose deprivation (OGD) or oxygen-glucose deprivation/reperfusion (OGD/R) injury. In vivo experiment, P7C3-A20 was administrated in middle cerebral artery occlusion (MCAO) rats and infarct volume was examined. Lastly, the brain tissue nicotinamide adenine dinucleotide (NAD) levels were detected in P7C3-A20 treated normal or MCAO mice.
Cell viability, morphology, and Tuj-1 staining confirmed the neuroprotective effect of P7C3-A20 in OGD or OGD/R model. P7C3-A20 administration significantly reduced cerebral infarction in MCAO rats. Moreover, brain NAD levels were elevated both in normal and MCAO mice after P7C3-A20 treatment.
P7C3-A20 has neuroprotective effect in cerebral ischemia. The study contributes to the development of NAMPT activators against ischemic stroke and expands the horizon of the neuroprotective effect of aminopropyl carbazole chemicals.
烟酰胺磷酸核糖转移酶(NAMPT)是缺血性中风的一个新的治疗靶点。本研究旨在探讨一种潜在的NAMPT激活剂P7C3 - A20(一种氨丙基咔唑衍生物)对缺血性中风的影响。
在体外研究中,通过将P7C3 - A20与遭受氧糖剥夺(OGD)或氧糖剥夺/再灌注(OGD/R)损伤的原代神经元共同孵育,研究其神经元保护作用。在体内实验中,对大脑中动脉闭塞(MCAO)大鼠给予P7C3 - A20,并检测梗死体积。最后,在P7C3 - A20处理的正常或MCAO小鼠中检测脑组织烟酰胺腺嘌呤二核苷酸(NAD)水平。
细胞活力、形态及Tuj - 1染色证实了P7C3 - A20在OGD或OGD/R模型中的神经保护作用。给予P7C3 - A20可显著减少MCAO大鼠的脑梗死面积。此外,P7C3 - A20处理后,正常和MCAO小鼠的脑NAD水平均升高。
P7C3 - A20对脑缺血具有神经保护作用。该研究有助于开发针对缺血性中风的NAMPT激活剂,并拓展了氨丙基咔唑类化合物神经保护作用的研究视野。