【摘要】：目的:探討鉀離子通道(TREK-1)阻滯劑SID1900對海馬區(qū)域突觸發(fā)生的調(diào)節(jié)作用及其可能的抗抑郁作用分子機制。方法:選用8~10周齡C57BL/6J雄性小鼠進行慢性不可預(yù)知溫和應(yīng)激(CUMS)造模,造模成功后給予TREK-1阻滯劑Spadin、SID1900連續(xù)28 d腹腔注射,分別于給藥0、7、14、21、28 d對小鼠進行行為學(xué)測試,通過Western blotting方法檢測突觸相關(guān)蛋白PSD95、Synapsin 1表達水平變化。結(jié)果:CUMS小鼠蔗糖水消耗百分比較對照組顯著降低,強迫游泳中不動時間顯著升高,出現(xiàn)抑郁樣表型;給藥3周后,Spadin、SID1900可以使CUMS小鼠蔗糖水消耗百分比升高,但較對照組仍然降低,對開場、強迫游泳實驗結(jié)果無顯著影響;給藥4周后,Spadin、SID1900使CUMS小鼠蔗糖水消耗百分比升高,且與對照組無差異,在強迫游泳、懸尾實驗中的不動時間縮短;Western blotting檢測顯示,給藥4周后CUMS小鼠突觸相關(guān)蛋白PSD95、Synapsin 1表達升高。結(jié)論:TREK-1阻滯劑SID1900可改善抑郁癥狀,使突觸相關(guān)蛋白PSD95、Synapsin 1表達升高,影響突觸發(fā)生可能是其抗抑郁作用機制之一。
[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.
【作者單位】： 東南大學(xué)醫(yī)學(xué)院;東南大學(xué)附屬中大醫(yī)院神經(jīng)內(nèi)科;
【基金】：國家自然科學(xué)基金青年科學(xué)基金資助項目(81402910)
【分類號】：R749.4
，

本文編號：2500483