氟西汀调控CUMS抑郁大鼠海马突触重塑

发布时间：2018-04-27 19:20

本文选题：氟西汀 + 抑郁　；参考：《中国病理生理杂志》2016年09期

【摘要】：目的:探究氟西汀(fluoxetine)对慢性不可预见性温和刺激(chronic unpredictable mild stress,CUMS)抑郁大鼠海马突触重塑的m TOR和细胞自噬信号调控作用。方法:60只雄性Sprague-Dawley大鼠随机分成正常对照(control)组、CUMS组和氟西汀组。采用CUMS结合孤养法构建CUMS抑郁模型,期间给予氟西汀(20 mg·kg-1·d-1)灌胃治疗。通过体重变化、糖水测试水平及行为学实验验证模型建立,采用RT-PCR和Western blotting等生化方法测定突触重塑相关蛋白胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)、突触泡蛋白(synaptophysin,SYP),细胞凋亡相关蛋白Bcl-2、cleaved caspase-3,m TOR信号通路相关蛋白m TOR、4EBP1,自噬相关蛋白beclin 1、LC3 mRNA及蛋白表达水平的变化。结果:与control组相比,CUMS大鼠的体重、糖水摄取量、旷场实验总路程和中间停留时间均下降,差异具有统计学显著性。RT-PCR和Western blotting实验结果显示,与control组相比,CUMS组SYP和GFAP的mRNA和蛋白水平显著下调,Bcl-2表达下调,cleaved caspases-3上调,m TOR及下游靶分子4EBP1磷酸化水平下调,细胞自噬关键基因beclin1和LC3在mRNA和蛋白水平显著上调。氟西汀可以减缓以上结果中的上调或下调趋势,差异具有统计学显著性。结论:氟西汀可能通过下调细胞凋亡和自噬信号通路以及上调m TOR信号通路调节海马突触重塑并缓解抑郁症状。
[Abstract]:Aim: to investigate the effects of fluoxetine on m TOR and autophagy signal regulation of hippocampal synaptic remodeling in chronic unpredictable mild stimulation of chronic unpredictable mild stress CUMS in depression rats. Methods 60 male Sprague-Dawley rats were randomly divided into control group and fluoxetine group. The depression model of CUMS was established by CUMS combined with solitary therapy, during which 20 mg kg-1 d -1 of fluoxetine was administered intragastric. The model was established by weight change, sugar water test level and behavioral experiment. RT-PCR and Western blotting methods were used to detect synaptic remodeling associated protein glial fibrillary acidic protein RT-PCR, synaptophysin Sysp, apoptosis-associated protein Bcl-2caspase-3caspase-3 TOR signaling pathway related protein m TOR4EBP1, autophagy associated protein beclin 1LC3 mRNA, and autophagy associated protein beclin 1LC3 mRNA. Changes in protein expression levels. Results: compared with the control group, the body weight, the intake of sugar water, the total distance and the middle residence time of the open field experiment were all decreased. The difference was statistically significant. The results of RT-PCR and Western blotting experiment showed that there was no significant difference between the two groups. Compared with control group, the mRNA and protein levels of SYP and GFAP in Cucms group were significantly down-regulated. The expression of Bcl-2 was down-regulated, and the expression of caspases-3 was down-regulated, and the phosphorylation level of 4EBP1 was down-regulated, and the key genes beclin1 and LC3 of autophagy were up-regulated in mRNA and protein levels. Fluoxetine can slow down the upward or downward trend of the above results, the difference is statistically significant. Conclusion: fluoxetine may regulate hippocampal synaptic remodeling and alleviate depression by down-regulating apoptosis and autophagy signaling pathway and up-regulating m TOR signaling pathway.
【作者单位】：嘉兴学院医学院;
【基金】：浙江省实验动物科技计划项目(No.2014C37019) 嘉兴市科技局项目(No.2015AY23066)
【分类号】：R749.4

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