cAMP/CREB/BDNF信号通路在沃替西汀抗小鼠抑郁样行为中的作用

目的：研究新型抗抑郁药沃替西汀对环磷酸腺苷/环磷酸腺苷反应元件结合蛋白/脑源性神经营养因子（cAMP/CREB/BDNF）信号转导通路的影响。方法将昆明小鼠随机分为对照组和慢性不可预知性温和应激（CUMS）造模组进行造模，采用糖水偏爱试验考察模型是否成功建立。造模结束后将CUMS组小鼠随机分为模型组、氟西汀组和沃替西汀组。采用悬尾试验、强迫游泳试验和旷场试验，考察沃替西汀对抑郁小鼠的抗抑郁作用。采用ELISA试剂盒检测小鼠海马组织中cAMP的含量。采用蛋白免疫印迹法检测小鼠海马组织中磷酸化CREB（pCREB）和BDNF的蛋白表达。结果沃替西汀显著缩短小鼠在悬尾和强迫游泳试验中的不动时间（P<0.01），而对其在旷场试验中的自主活动行为没有影响（P>0.05），表明沃替西汀可改善抑郁小鼠的抑郁样行为；ELISA结果显示沃替西汀能显著增加小鼠海马组织内cAMP的含量（P<0.01）；蛋白免疫印迹结果表明沃替西汀可以促进pCREB和BDNF的蛋白表达（P<0.01）。结论沃替西汀产生抗抑郁作用机制可能与影响cAMP/CREB/BDNF信号转导通路有关。

Role of cAMP/CREB/BDNF signaling pathway in anti-depressive effect of vortioxetine in mice

Objective To investigate the effects of vortioxetine on cAMP/CREB/BDNF signal pathway. Methods Forty Kunming mice were randomized into control group and chronic unpredictable mild stress (CUMS) group. After establishment of depres-sive models verified by sucrose preference test, the mice in CUMS group were divided into model group, fluoxetine group and vortioxetine group. The antidepressive effect of vortioxetine was analyzed by tail suspension test, forced swim test and open field test. The levels of cAMP were detected using a commercial ELISA kit, and the expressions of pCREB and brain-derived neurotrophic factor (BDNF) were evaluated with Western blotting. Results Vortioxetine significantly shortened the immobility time of the depressive mice in tail suspension test and forced swim test without affecting the locomotor activity of the mice in open fields, suggesting the antidepressive effect of against depression in mice. Vortioxetine significantly increased the levels of cAMP and promoted the expression of pCREB and BDNF in the hippocampus of the mice (P<0.01). Conclusion Vortioxetine improves the behaviors of mice with depression possibly by affecting the cAMP/CREB/BDNF signal pathway.