迷迭香酸基于AKT/mTOR通路促进抑郁模型大鼠海马神经元再生  

Rosmarinic Acid Induces Hippocampal Neurogenesis on Chronic Depression Rats through AKT/mTOR Signaling Pathway

作　　者：曹晓品 赵美霞 梁承磊 CAO Xiao-pin;ZHAO Mei-xia;LIANG Cheng-lei(Xuyi Chinese Medicine Hospital,Xuyi 210000,China)

机构地区：[1]盱眙县中医院药剂科,江苏盱眙211700

出　　处：《海峡药学》2022年第3期39-45,共7页Strait Pharmaceutical Journal

摘　　要：目的 探讨迷迭香酸是否基于AKT/mTOR通路促进大鼠海马神经元再生。方法 构建SD大鼠抑郁模型,腹腔注射迷迭香酸或盐酸帕罗西汀28天。应激结束观察各组大鼠行为学指标改变。检测大鼠海马神经生长因子(NGF)、神经元特异性烯醇化酶(NSE)的表达差异及BrdU、NSE的比例。建立皮质酮诱导原代海马神经元细胞损伤模型,通过MK-2206阻断AKT通路,检测给予迷迭香酸后神经元存活率,测定各组AKT、p-AKT、mTOR、p-mTOR蛋白表达。结果 迷迭香酸组大鼠的行为学指标得到显著改善。NGF、NSE的表达显著升高,BrdU与NSE的比例增加。迷迭香酸能够明显改善皮质酮损伤导致的神经元再生,阻断AKT/mTOR后,可拮抗其对神经元的保护作用。结论 迷迭香酸可通过AKT/mTOR通路促进神经元再生,保护海马神经元,发挥抗抑郁作用。OBJECTIVE Investigate the anti-depressant mechanism of rosmarinic acid(RA) in chronic depression rats based on AKT/mTOR signaling pathway.METHODS Rats subjected to unpredictable chronic mild stress(UCMS) were used as depression model,intraperitoneal injected by rosmarinic acid or paroxetine hydrochloride for 28 days.After the end of the treatment,observe the changes in the behavioral indicators of the rats in each group.The expression of nerve growth factor(NGF) and neuron-specific enolase(NSE) protein in hippocampus of each group was analyzed by immunohistochemistry and real time PCR,the ratio of BrdU to NSE was analyzed by immunofluorescence.The primary cultured hippocampal neurons were induced by corticosterone as cell damage model.We analysis the the survival rate of neurons after treatment by rosmarinic acid and the AKT inhibitor MK-2206.Western blot was used to detect AKT,p-AKT,mTOR,p-mTOR expression levels of primary cultured hippocampal neurons treated by RA and MK-2206.RESULTS After 28 days of chronic stress,the spontaneous activity and sugar consumption of the model group were significantly reduced,and the forced swimming time was significantly increased.After treatment with rosmarinic acid in chronically stressed rats,we found the protein level and mRNA levels of NGF and NSE in hippocampus were increased,the ratio of BrdU to NSE increased by treated with rosmarinic acid.Corticosterone treatment reduced the cell proliferation in cultured neurons in vitro,rosmarinic acid co-culture for 18 hours can significantly improve the neuronal regeneration and increase the p-AKT and p-mTOR expression.After primary neuronal cells were treated with MK-2206,AKT pathway inhibitor,the effect of rosmarinic acid on increasing the expression of p-AKT and p-mTOR was inhibited.CONCLUSION Rosmarinic acid can promote neuron regeneration through the AKT/mTOR pathway,thus exerting antidepressant effects.

关 键 词：抑郁症 迷迭香酸 AKT/mTOR信号通路 神经元再生 

分 类 号：R965[医药卫生—药理学]