度洛西汀对小脑颗粒神经元谷氨酸毒性作用的保护作用及机制  被引量:1

Protective effect of Duloxetine on glutamate toxicity of cerebellar granule neurons and its mechanism

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作  者:柳四新 何丹 余孝君 王家祺 

机构地区:[1]长沙市第一医院神经内2科,湖南长沙410005

出  处:《中国医药导报》2016年第33期30-33,共4页China Medical Herald

摘  要:目的观察度洛西汀对小脑颗粒神经元谷氨酸毒性作用的保护作用及机制。方法体外培养CD-1小鼠小脑颗粒神经元,神经元细胞随机分为8组:对照组,谷氨酸组,度洛西汀组,度洛西汀+谷氨酸组,SB204741处理组,SB204741+谷氨酸组,LY294002处理组,LY294002+谷氨酸组。采用TUNEL法检测神经元细胞凋亡程度,采用共聚焦显微镜fura-2探针检测神经元内Ca^(2+)水平。结果与对照组比较,谷氨酸毒性能明显增加神经元凋亡[(1.62±0.96)比(13.98±3.49)](P<0.05),度洛西汀显著抑制由谷氨酸毒性引起的神经元凋亡。度洛西汀能降低由谷氨酸毒性激活的神经元内Ca^(2+)升高。5-HT_(2B)SB204741能抑制由谷氨酸毒性引起的神经元凋亡和神经元内Ca^(2+)升高,而LY294002只能抑制谷氨酸毒性引起的神经元凋亡,对于谷氨酸毒性引起的神经元内Ca^(2+)升高无作用。结论度洛西汀具有抵抗神经元谷氨酸毒性作用,其机制主要是通过5-HT_(2B)受体活化细胞内钙库释放,从而引起EGFR间接激活PI3K/AKT/m TOR通路,抑制由谷氨酸毒性引起的神经元凋亡。Objective To observe the protective effect of Dnloxetine on glutamate toxicity of cerebellar granule neurons and its mechanism. Methods The cerebellar granule neurons derived from CD-1 mice were cultured in vitro, all the neurons were randomly divided into eight groups: control group, glutamate group, Duloxetine group, Duloxetine+gluta- mate group, SB204741 treatment group, SB204741+glutamate group, LY294002 treatment group, LY294002+glutamate group. The apoptosis degrees of neurons were detected by TUNEL method, the levels of Ca2+ in neurons were detected by confoeal microscopy fura-2. Results Compared with control group, glutamate toxicity could significantly increase the neuron apoptosis [(1.62±0.96) vs (13.98±3.49)] (P 〈 0.05), and Duloxetine could inhibit the neuron apoptosis caused by glutamate toxicity. Duloxetine could significantly decrease the increasing concentration of Ca〉 in neurons activated by glutamate toxicity. 5-HT2B SB204741 could significantly inhibit the neuron apoptosis and the increasing concentration of" Ca^2+ in neurons caused by glutamate toxicity, while LY294002 could only inhibit the neuron apoptosis caused by glutamate toxicity, which had no effects on the increasing concentration of Ca^2+ in neurons activated by glutamate toxicity. Conclusion Duloxetine has the effects of inhibiting the glutamate toxicity of neurons, the main mechanism may be associated with the release of intracellular calcium store activated by the receptor of 5-HT2R, which cause EGFR activating PI3K/AKT/mTOR signal pathway indirectly, so as to inhibit the neuron apoptosis caused by glutamate toxicity.

关 键 词:度洛西汀 谷氨酸毒性 神经元 

分 类 号:R971[医药卫生—药品]

 

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