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TREK-1阻滞剂SID1900对CUMS小鼠突触发生的调节作用

发布时间:2019-06-15 20:18
【摘要】:目的:探讨钾离子通道(TREK-1)阻滞剂SID1900对海马区域突触发生的调节作用及其可能的抗抑郁作用分子机制。方法:选用8~10周龄C57BL/6J雄性小鼠进行慢性不可预知温和应激(CUMS)造模,造模成功后给予TREK-1阻滞剂Spadin、SID1900连续28 d腹腔注射,分别于给药0、7、14、21、28 d对小鼠进行行为学测试,通过Western blotting方法检测突触相关蛋白PSD95、Synapsin 1表达水平变化。结果:CUMS小鼠蔗糖水消耗百分比较对照组显著降低,强迫游泳中不动时间显著升高,出现抑郁样表型;给药3周后,Spadin、SID1900可以使CUMS小鼠蔗糖水消耗百分比升高,但较对照组仍然降低,对开场、强迫游泳实验结果无显著影响;给药4周后,Spadin、SID1900使CUMS小鼠蔗糖水消耗百分比升高,且与对照组无差异,在强迫游泳、悬尾实验中的不动时间缩短;Western blotting检测显示,给药4周后CUMS小鼠突触相关蛋白PSD95、Synapsin 1表达升高。结论:TREK-1阻滞剂SID1900可改善抑郁症状,使突触相关蛋白PSD95、Synapsin 1表达升高,影响突触发生可能是其抗抑郁作用机制之一。
[Abstract]:Aim: to investigate the regulatory effect of potassium channel (TREK-1) blocker SID1900 on synapsis in hippocampal region and its possible antidepressant molecular mechanism. Methods: 8 脳 10 week old C57BL/6J male mice were used to model chronic unpredictable mild stress (CUMS). After successful establishment, TREK-1 blocker Spadin,SID1900 was injected intraperitoneally for 28 days. The mice were given behavioral test at 0, 7, 14, 21 and 28 days, respectively, and the expression of synaptic related protein PSD95,Synapsin 1 was detected by Western blotting method. Results: compared with the control group, the percentage of sucrose water consumption in CUMS mice was significantly lower, the immobility time in forced swimming was significantly increased, and the depressive phenotype appeared. After 3 weeks of administration, Spadin,SID1900 could increase the percentage of sucrose water consumption in CUMS mice, but it was still lower than that in the control group, but had no significant effect on the results of forced swimming experiment. After 4 weeks of administration, Spadin,SID1900 increased the percentage of sucrose water consumption in CUMS mice, which was not different from that in the control group.; Western blotting showed that the expression of synaptic related protein PSD95,Synapsin 1 in CUMS mice increased after 4 weeks of administration. Conclusion: TREK-1 blocker SID1900 can improve depressive symptoms and increase the expression of synaptic associated protein PSD95,Synapsin 1, which may be one of the mechanisms of its antidepressant effect.
【作者单位】: 东南大学医学院;东南大学附属中大医院神经内科;
【基金】:国家自然科学基金青年科学基金资助项目(81402910)
【分类号】:R749.4


本文编号:2500483

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