川芎嗪对急性和慢性应激抑郁模型大鼠抗抑郁样作用的实验研究

目的 探讨川芎嗪的抗抑郁作用.方法 采用强迫游泳实验制备急性应激大鼠抑郁模型,长期轻度应激+孤养制备大鼠慢性抑郁模型.慢性应激实验采用SD雄性大鼠,基于糖水摄入实验结果随机分为对照组、模型(慢性应激)组、阳性对照(慢性应激+氟西汀)组和川芎嗪(慢性应激+不同剂量川芎嗪)组,每组13或14只动物.氟西汀(2.0mg·kg-1·d-1)和川芎嗪灌胃(10,20,40mg·kg-1·d-1),持续28d.对照组不予任何刺激.慢性应激期间测定动物的体质量和摄食量,旷场行为、液体消耗试验检查动物行为和液体消耗(糖水偏爱)的变化,实验末行强迫游泳实验.结果 短期应用川芎嗪组大鼠强迫游泳(急性抑郁)不动时间(89.0±37.0)s]明显缩短对照组为(117.1±32.1)s,P<0.05].川芎嗪部分逆转慢性应激引起的动物的抑郁表现.实验第4周末,与模型组比,川芎嗪(40mg/kg×28)组液体总消耗和糖水消耗量显著增加(P<0.05),糖水偏爱百分比升高,水平运动得分增加,慢性抑郁期强迫游泳不动时间(91.9±31.5) s]显著缩短模型组为(124.4±27.0)s,P<0.05].结论 川芎嗪有明显的抗抑郁样作用.

Antidepressant-like activity of tetramethylpyrazine measured by acute and chronic experimental methods in rat model of depression

Objective To study the potential antidepressive-like effect of tetramethylpyrazine (TMP). Methods Forced-swimming and chronic mild stress (CMS) tests were performed to assess the antidepressant-like activity of TMP. Male Sprague-Dawley (SD) strain rats were divided into six matched groups (n= 13 or 14 in each group) based on their sucrose consumption:control, CMS, CMS + fluoxetine, and CMS + TMP groups. The rats except control were housed separately in different rooms, and the rat model of depression was established by exposing to an unpredictable sequence of stressors for 28 days; the rats in CMS + fluoxetine were exposed to CMS and received administration of FLU (2.0 mg· kg-1·d-1 ,ig) for 28 days; the rats in CMS + TMP groups were exposed to CMS and received administration of TMP (10,20,40 mg·kg-1·d-1 ,ig) , respectively, for 28 days. The rats in control group were given ordinary daily care and received ig administration of normal saline simultaneously. The body weight, food intake and fluid consumption were measured, and the behaviors were examined by open field during the duration of the stress procedure, and forced-swimming test was performed 1 day after last unpredictable stressor. Results Acute administration of TMP markedly decreased the duration of immobility during forced-swimming test((89.0 ±37.0)s vs (117.1 ±32. 1)s, P<0.05) . Chronic administration of TMP partially countered the effects of CMS on consumption of sucrose solution and locomotion and exploration behavior, and potently shortened the immobility time during forced-swimming test following CMS in rats. The results showed that long-term administration of TMP partially reversed the effects of CMS on the body weight gain,the consumption of sucrose solution,the squares crossing in open field test and the immobility time during forced-swimming test in rats ((91.9 ±31.5) vs (124.4±27.0)s,P<0.05).Conclusion TMP shows obvious antidepressant-like activity.