山奈酚对乳腺癌抑郁模型大鼠的抗抑郁作用研究

Antidepressant Effect of Kaempferol on Rat Complex Model of Depression and Breast Cancer

目的探讨山奈酚对实验性乳腺癌抑郁大鼠的抗抑郁作用。方法 90只大鼠随机分为对照组、乳腺癌组、抑郁组、复合模型组、氟西汀组、山奈酚组,每组15只。通过慢性不可预知性轻度应激方法建立大鼠抑郁模型,以二甲基苯蒽为诱导剂建立乳腺癌大鼠模型。采用旷场实验垂直运动次数及水平活动总路程观察各组大鼠自主活动;液质联检分析各组大鼠脑内海马及前额叶皮质单胺类神经递质,包括去甲肾上腺素(norepinephrine,NE)、多巴胺(dopamine,DA)和5-羟色胺(5-hydroxytryptamine,5-HT)含量的变化。结果乳腺癌组自主活动均减少,但与对照组比较无显著性差异;抑郁组和复合模型组自主活动减少,与对照组比较差异均有显著性(P<0.01);与复合模型组相比,山奈酚组与氟西汀组垂直运动次数及水平活动总路程均显著增加(P<0.05或P<0.01)。与复合模型组比较,氟西汀组海马区DA、5-HT含量显著增高(P<0.01),前额叶皮质DA、NE、5-HT浓度均显著性增高(P<0.05);山奈酚组与复合模型组比较,海马部位NE含量明显增高(P<0.05),前额叶皮质部位DA、NE、5-HT浓度均显著性增高(P<0.05或P<0.01)。结论山奈酚具有显著抗大鼠抑郁作用,可能通过提高前额叶皮质部位NE、DA、5-HT递质水平达到抗抑郁作用。

OBJECTIVE To study the antidepressant effect of kaempferol on rat complex model of depression and breast cancer. METHODS The rats were randomly divided into six parts including the control group, depression model group, breast cancer model group, complex model group, fluoxetine administration group, kaempferol administration group, respectively. The rat depression model was established by the method of chronic unpredictable mild stress. The breast cancer model was induced by dimethylbenzanthracine（DMBA）. The open filed test was used to evaluate the autonomic activities. The LC-MS/MS method was used to assay the levels of monoamine neurotransmitters including norepinephrine（NE）, serotonin（5-HT） and dopamine（DA） in the hippocampal area and the prefrontal cortex. RESULTS There were no significant differences in the open-field test between the cancer group and normal group, whereas the open-field activities decreased significantly in the depression model group and complex model group including horizontal movements and vertical movements with comparison to the normal group（P〈0.01）. The autonomic activities increased significantly after kaempferol administration（P〈0.01 or P〈0.05）. The antidepressant-like effect of kaempferol was similar to fluoxetine with respect to increasing the autonomic activities. The levels of NE, DA and 5-HT in the brains of the depression model and complex model showed to decrease comparing to the control group. Whereas the levels of those in kaempferol administration group were higher than those in the complex model group. And the levels of DA, NE and 5-HT in the prefrontal cortex were significantly increased（P〈0.01 or P〈0.05）. These changes were almost observed in fluoxetine administration group. CONCLUSION The study suggested that kaempferol showed antidepressant effects on rat complex model of depression and breast cancer. The underling mechanism of kaempferol antidepressant effect may be associated with increased the level of monoamine neurotransmitters in rat prefrontal lobe.