Ye Wen, Yan Yan, Tang Yunliang, Dong Xiaoyang, Chen Gengfa, Kang Junwei, Huang Lianghua, Xiong Qi, Feng Zhen
Department of Rehabilitation, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People's Republic of China.
Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People's Republic of China.
J Inflamm Res. 2021 May 18;14:2007-2017. doi: 10.2147/JIR.S308078. eCollection 2021.
Neuronal damage is the main cause of neurological diseases. Neural stem cells (NSCs) have the functions of cell repair and replacement of neurons, secretion of neurotrophic factors, and immune regulation of the neural microenvironment.
Previous study found that Orexin-A had a protective effect on neurons in the central nervous system, but it is lacking in making great efforts on the function of Orexin-A on NSCs. This study aimed to investigate the anti-inflammatory responses and signaling mechanisms of Orexin-A on lipopolysaccharide (LPS)-induced NSCs.
Quantitative real-time polymerase chain reaction was used to detect the mRNA level. Signaling pathway-related protein expression was detected by Western blot. The proliferation and migration of NSCs were investigated by Cell Counting Kit-8 (CCK-8) detection kit and transwell assay. Besides, the staining of hematoxylin and eosin (HE) was performed to study the morphology of cell.
Orexin-A decreased the pro-inflammatory cytokines of IL-1β, TNF-α, and IL-6 induced by LPS by regulating nuclear factor-k-gene binding (NF-kB) and phosphorylation of P38/Erk-mitogen-activated protein kinases (MAPKs) pathways, but not p-JNK signaling.
Our findings indicate that Orexin-A can alleviate the inflammatory response of NSC. It can provide beneficial help in neural stem cell therapy applications.
神经元损伤是神经疾病的主要病因。神经干细胞具有细胞修复和替代神经元、分泌神经营养因子以及对神经微环境进行免疫调节的功能。
前期研究发现食欲素A对中枢神经系统的神经元具有保护作用，但在食欲素A对神经干细胞功能方面的研究较少。本研究旨在探讨食欲素A对脂多糖诱导的神经干细胞的抗炎反应及信号机制。
采用定量实时聚合酶链反应检测mRNA水平。通过蛋白质免疫印迹法检测信号通路相关蛋白表达。采用细胞计数试剂盒-8检测试剂盒和Transwell实验检测神经干细胞的增殖和迁移。此外，进行苏木精-伊红染色以研究细胞形态。
食欲素A通过调节核因子-k基因结合和P38/细胞外信号调节激酶丝裂原活化蛋白激酶通路的磷酸化来降低脂多糖诱导的白细胞介素-1β、肿瘤坏死因子-α和白细胞介素-6等促炎细胞因子，但不影响磷酸化c-Jun氨基末端激酶信号。
我们的研究结果表明食欲素A可以减轻神经干细胞的炎症反应。它可为神经干细胞治疗应用提供有益帮助。
