阿魏酸钠的神经保护和神经发生增强作用  

Neuroprotective and Neurogenesis-enhancing Effects of Sodium Ferulate

作　　者：廖铭能[1] 王艳平[1] 张永平[1] 马润娣[1] 张霄瑜 于立坚[1] 于廷曦[1,3] 

机构地区：[1]广东海洋大学海洋药物研究与开发重点实验室,湛江524025 [2]Department of Otorhinolaryngology-Head and Neck Surgery,University of Maryland School of Medicine,baltimoremd21228 [3]Cell Biology Group,Department of Surgery,Department of Pathology,University of Maryland School of Medicine and Baltimore Veterans Affairs Medical Center,baltimoremd21201

出　　处：《中国细胞生物学学报》2010年第6期840-849,共10页Chinese Journal of Cell Biology

摘　　要：作用靶点新颖而又无副作用的抗抑郁药正处于巨大需求之中。阿魏酸(ferulic acid,FA)是一种广泛存在的低毒酚酸,阿魏酸钠(sodium ferulate,SF)则是其钠盐。我们先前的研究已经表明,阿魏酸具有显著的抗兴奋性中毒和抗抑郁样作用,而我们现在则研究其神经保护和神经发生增强效果,并讨论其神经保护和神经发生增强效果与它的抗抑郁样作用的关系。MTT法检测阿魏酸钠对PC12细胞生长的影响和它的神经保护作用;形态学和免疫细胞化学方法检测其诱导分化作用;免疫组织化学和BrdU-掺入方法检测抑郁症样模型大鼠海马神经生长因子(nerve growth factor,NGF)和脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的表达水平及神经干细胞/神经前体细胞的增殖状况。体外试验表明,阿魏酸钠促进PC12细胞的增殖,部分保护PC12细胞免受过氧化氢(H_2O_2)和地塞米松(dexamethasone,DXM)诱导的损伤,诱导PC12细胞分化为形态特征和分子标记与神经样细胞一致的细胞。体内试验表明,阿魏酸钠上调NGF和BDNF的表达,增强抑郁症样模型大鼠海马神经干细胞/神经前体细胞的增殖。上述研究提供的证据表明,阿魏酸钠具有神经保护和神经发生增强作用,而阿魏酸钠的抗抑郁样效果可能系其神经保护和神经发生增强作用所致。Antidepressants with novel targets and without side effects are in great demand.Ferulic acid （FA） is a ubiquitous phenolic acid of low toxicity,and sodium ferulate（SF） is its sodium salt.Our previous studies have revealed that FA（or SF） show significant protective effect on excitotoxicity and antidepressant-like effect,and we now test the neuroprotective and neurogenesis-enhancing actions of SF and discuss their relationship with its antidepressant-like effect of SF.MTT assay was performed to measure the effect of SF on the growth of PC12 cells and its neuroprotective effects;morphological and immunocytochemical methods were used for assessing its differentiation-inducing action.The expressions of nerve growth factor（NGF） and brain-derived neurotrophic factor（BDNF） and the proliferation of neural stem cell/neural progenitor cells were assessed in the hippocampi of chronic mild stress（CMS）-induced depression-like model rats by immunohistochemistry and BrdU-incorporation assays.In vitro tests showed that SF promoted the proliferation of PC12 cells in the concentration range of 5～320 mmol/L,and partially protected PC12 cells against H_2O_2-induced oxidative and dexamethasone（DXM）-induced neurotoxicity damage,and induced PC12 cells to differentiate to more mature cells with the morphological characteristics and molecular marker of neuronal-like cells.In vivo tests showed that SF up-regulated the expressions of NGF and BDNF,and induced the proliferation of neural stem cell/neural progenitor cells in the hippocampi of CMS-induced depression-like model rats.This study provides evidences that SF shows the neuroprotective and neurogenesis-enhancing actions,and the antidepressant-like effects of SF may result from its neuroprotective and neurogenesis-enhancing actions.

关 键 词：阿魏酸钠 神经保护作用 神经发生增强作用 PC12细胞 抑郁症大鼠模型 

分 类 号：R285.5[医药卫生—中药学]