阿魏酸钠诱导分化的PC12细胞裂解液的无细胞滤液的抗抑郁样效果  

Antidepressant-like Effect of Cell-free Filtrate of Sodium Ferulate-induced and Differentioned PC12 Cell Lysates

作　　者：廖铭能[1] 于立坚[1] 张永平[1] 马润娣[1] 张霄瑜[1,2] 于廷曦[1,3] 

机构地区：[1]广东海洋大学海洋药物重点实验室 [2]Department of Otorhinolaryngology-Head and Neck Surgery,University of Maryland School of Medicine,MD 21228 [3]Cell Biology Group,Department of Surgery,Department of Pathology,University of Maryland School of Medicine and Baltimore Veterans Affairs Medical Center,MD 21201

出　　处：《中国细胞生物学学报》2011年第6期608-621,共14页Chinese Journal of Cell Biology

基　　金：广东海洋大学研究生基金资助项目~~

摘　　要：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。先前的研究已经证实,阿魏酸钠具有显著的神经保护和神经发生增强作用及抗抑郁效果。该研究的目的在于探讨阿魏酸钠诱导分化的PC12细胞裂解液的无细胞滤液可能的抗抑郁效果。PC12细胞在含80μmol/L阿魏酸钠的DMEM培养基中孵育6d,无菌条件下制备阿魏酸钠诱导分化的PC12细胞液的无细胞滤液,测定PC12细胞裂解液无细胞滤液中残留的阿魏酸钠量。以慢性不可预期的多种刺激制造大鼠抑郁模型,用行为学、形态学、免疫组织化学和BrdU掺入等方法观察并检测阿魏酸钠诱导分化的PC12细胞裂解液的无细胞滤液对慢性应激大鼠抑郁模型行为学、海马的组织病理学、海马和大脑皮质的神经生长因子(nerve growth factor,NGF)及脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的表达及神经发生的影响。实验证实,阿魏酸钠诱导分化的PC12细胞裂解液的无细胞滤液能改善抑郁症样模型大鼠的行为学障碍,上调其海马和大脑皮质NGF和BNDF的表达,增加海马神经干细胞/神经前体细胞的增殖。由此可见,阿魏酸钠诱导分化的PC12细胞裂解液的无细胞滤液有明显的抗抑郁效果,而其抗抑郁效果可能源自它的上调NGF和BNDF,以及其增强神经发生作用。Ferulic acid （FA）, 3-（4-hydroxy-3-methoxyphenyl）-2-propenoic acid, is one of the most common phenolic acids with low toxicity, and sodium ferulate （SF） is its sodium salt. Our previous work demonstrates that SF has significant neuroprotective and neurogenesis-enhancing actions and antidepressant-like effects. The aim of this study was to investigate a potential antidepressant-like effect of cell-free filtrate of sodium ferulate-induced and differentioned PC12 cell lysates （SFIDPC12CL） in the chronic mild stress （CMS）-induced depression-like model rats. PC12 cells were cultured in DMEM containing 80 ~tmol/L SF for 6 days, and then cell-free SFIDP-C12CL was prepared. Residual SF concentration in cell-free SFIDPC12CL was assayed by HPLC. Depression-like rat models were reproduced by CMS stimuli. Antidepressant effects of SFIDPC12CL were assessed by behav-ioural tests. The effects of SFIDPC12CL on hippocampal and cerebral cortex expressions of nerve growth factor （NGF） and brain-derived neurotrophic factor （BDNF） were assayed by immunohistochemistry, and the effect of SFIDPC12CL on hippocampal neurogenesis assayed using the thymidine analog bromodeoxyuridine （BrdU） as a marker for dividing cells in CMS-induced depression-like model rats. Our studies demonstrate that administration of SFIDPC 12CL significantly attenuated the CMS-induced depression-like behavioural disorders, up-regulated the hippocampal and cerebral cortex expressions of NGF and BDNF, and increased the hippocampal number of BrdU-labeled cells. These findings indicate that SFIDPC12CL shows marked antidepressant-like effects in the CMS-induced depression-like model rats, and raise the possibility that SFIDPC12CL up-regulates expressions of NGF and BDNF, and increases neuronal number.

关 键 词：阿魏酸钠 PC12细胞 诱导分化 细胞裂解液 抗抑郁样效果 慢性抑郁模型 大鼠 

分 类 号：R96[医药卫生—药理学]