西酞普兰对抑郁模型大鼠的治疗作用及机制研究

摘要

目的 通过连续腹腔注射西酞普兰,研究西酞普兰对慢性不可预知性应激(chronic unpredicted stress,CUS)抑郁模型大鼠的保护作用及相关机制.方法 1)建立慢性不可预知性应激大鼠抑郁模型,采用包括束缚、强迫游泳、禁食水、夹尾等多种方法连续刺激成年雄性SD大鼠4周,检测其抑郁行为.2)模型成功后,对模型组大鼠连续腹腔注射不同剂量西酞普兰3周,观察大鼠行为学的改善.3)行为学检测后,将大鼠立即处死,采用ELISA和Western blotting的方法检测血清和海马中脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的含量.结果 1)慢性不可预知性应激4周后,模型组大鼠体质量降低,糖水偏好明显下降,旷场实验垂直和水平运动距离明显减少,提示造模成功.2)给药3周后,10 mg·kg-1·d-1西酞普兰能够明显提高模型组大鼠糖水偏好及旷场实验垂直和水平运动距离,提示抑郁症状得到改善.3)10 mg·kg-1·d-1西酞普兰组模型大鼠血清和海马BDNF含量与模型组相比显著升高.结论 慢性不可预知性应激4周可使大鼠出现抑郁症状,10 mg· kg-1 ·d-1西酞普兰可以改善模型大鼠的抑郁行为,其机制可能与提高了海马BDNF的含量相关.%Objective To explore the protective effect of citalopram on depressive model rats and the relative mechanism through continuous intraperitoneal injection of citalopram. Methods Establishing chronic unpredictable stress rat model. It consisted of a variety of stressors applied randomly every day for 4 weeks, The type of stressor included restraint, forced swim, food or water deprivation, tail pinch and so on. Successful model rats were subjected to continuous intraperitoneal injection with different doses of citalopram for 3 weeks, followed by behavioral tests. Sacrificing the rats immediately after the last behavioral test, the content of brain-derived neurotrophie factor ( BDNF) in the hippocampus and serum was detected by ELISA and Western Blotting. Results After chronic unpredictable stress for 4 weeks, the model rats displayed lower weight gain, decreased sucrose preference, and reduced locomotor activity. Intraperitoneal injection with 10 mg· kg-1 · d-1 citalopram for 3 weeks could significantly increase the sucrose preference and the movement distance of model rats. Intraperitoneal injection with 10 mg · kg-1 · d-1 citalopram for 3 weeks could significantly increased the content of BDNF in the serum and the hippocampus of model rats. Conclusion Rats subjected to chronic unpredictable stress for 4 weeks displayed apparent depressive symptoms. Intraperitoneal injection with 10 mg · kg-1 · d-1 citalopram for 3 weeks could improve the depressive behavior of model rats, the underlying mechanism may relate to increased BDNF content in the hippocampus.