仙茅苷对学习无助抑郁模型小鼠海马细胞凋亡的作用及其机制研究
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国家自然科学基金项目(81673716,81601181);安徽省自然科学基金项目(1808085J15)


Effect of Curculigoside on the Apoptosis of Hippocampal Neurons in a Mouse Model of Learned Helplessness and Related Mechanisms
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    摘要:

    目的 研究仙茅苷对学习无助抑郁模型小鼠海马细胞凋亡的作用及其机制。方法 给予仙茅苷预处理,建立小鼠学习无助模型,用行为学实验评估其抑郁样行为,脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TdT-mediated dUTP nick-end labeling,TUNEL)检测海马区细胞凋亡数,免疫荧光法检测海马区胶质原纤维酸性蛋白(glial fibrillary acidic protein,GFAP)荧光强度,免疫印迹法检测海马齿状回(dentate gyrus,DG)区相关蛋白的表达水平。结果 仙茅苷能明显缩短学习无助模型小鼠强迫游泳和悬尾试验中的不动时间(P<0.05),减少其海马DG区的神经细胞凋亡的数量(P<0.05),减弱其星形胶质细胞活化(P<0.05),促进蛋白激酶A磷酸化水平和突触后密度蛋白95的表达(P<0.05)。结论 仙茅苷在学习无助诱导的抑郁样行为中具有保护作用,可能是通过促进蛋白激酶A通路,减少海马DG区的颗粒细胞凋亡和抑制星形胶质细胞活化来介导的。

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    Objective To investigate the effect of curculigoside (CUR) on the apoptosis of hippocampal neurons in a mouse model of learned helplessness and related mechanisms. Methods CUR pretreatment was given to experimental mice, and a mouse model of learned helplessness was established. Behavioral experiment was used to evaluate depression-like behaviors; terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to measure the number of apoptotic neurons in the hippocampus; immunofluorescence assay was used to measure the fluorescence intensity of glial fibrillary acidic protein (GFAP) in the hippocampus; Western blotting was used to measure the expression of related proteins in the hippocampal dentate gyrus. Results CUR significantly shortened the immobility time in forced swimming test and tail suspension test (P<0.05), decreased the number of apoptotic neurons in the hippocampal dentate gyrus (P<0.05), reduced the activation of astrocytes (P<0.05), and promoted the phosphorylation of protein kinase A and the expression of postsynaptic density protein-95 (P<0.05). Conclusion CUR exerts a protective effect against depression-like behaviors induced by learned helplessness, possibly by promoting the protein kinase A signaling pathway, reducing neuronal apoptosis in the hippocampal dentate gyrus, and inhibiting the activation of astrocytes.

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申丰铭,杨三娟,张峥嵘,朱国旗.仙茅苷对学习无助抑郁模型小鼠海马细胞凋亡的作用及其机制研究[J].安徽中医药大学学报,2019,38(6):38-43

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  • 在线发布日期: 2019-11-25