槟榔十三味丸(高尤-13)对慢性应激抑郁大鼠行为学及海马神经元凋亡的影响

Effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pill on Behavior and Apoptosis of Hippocampal Cells in Depressive Rats

目的:观察槟榔十三味丸(高尤-13)对慢性应激抑郁模型大鼠行为学及海马神经元凋亡的影响,以期从细胞水平探讨该方抗抑郁症作用机制。方法:将48只Wistar雄性大鼠,根据蔗糖水消耗量及体质量随机分为正常对照组,模型组,氟西汀组(3.3 mg·kg-1),槟榔十三味丸低剂量组、中剂量组、高剂量组(0.25 g·kg-1,0.5 g·kg-1,1.0 g·kg-1),共6组,每组8只。除正常对照组外,其余大鼠均采用慢性轻度不可预见性应激结合孤养方法制备抑郁模型,造模同时灌胃给药,每日1次,连续给药28 d。以敞箱实验、蔗糖水消耗实验进行行为学评价,采用膜联蛋白V-异硫氰酸荧光素/碘化丙啶双标记(AnnexinVFITC/PI),以流式细胞仪(FC)检测海马神经元凋亡率。结果:与正常对照组比较,模型组大鼠水平运动及垂直运动得分、体质量、蔗糖水消耗量显著降低(P<0.01);与模型组比较,氟西汀组,槟榔十三味丸中剂量组、高剂量组大鼠水平运动及垂直运动得分、糖水消耗量、体质量均显著增加(P<0.05);流式细胞仪检测凋亡率显示,与正常对照组比较,模型组大鼠海马神经元凋亡率显著增高(P<0.05);与模型组比较,氟西汀组,槟榔十三味丸中剂量组、高剂量组大鼠海马神经元凋亡率降低,差异有显著性(P<0.01)。结论:慢性应激抑郁模型大鼠存在行为学异常及海马神经元凋亡现象,槟榔十三味丸能改善抑郁模型大鼠行为学异常及抑制慢性应激造成的大鼠海马神经元凋亡而发挥抗抑郁作用。

Objective： To study the effect of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pill on behavior and apoptosis of hipp- ocampal cells in depressive rats and from the cell level to discuss antidepressant mechanism. Methods ：48 male Wistar rats were random- ly divided into six groups according to the sugar consumption test and body weight（8 rats in each group） ：normal control group,model group, Fluoxetine group （ 3.3 mg · kg^-1 ） and high, medium and low dose group （0.25,0.5,1.0 g · kg^- 1 ） of Betel Shisanwei ingredi- ents Pill. Except the normal control, the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely raising. Intragastric administration, once daily, continuously for 28 days. Behavior changes of rats were detected through open？ field test, and sugar consumption test were also measured by AnnexinV - FITC/PI double labeling. Flow Cytometer was used to detectthe apoptotic rats in the hippocampus. Results ： Compared with normal control group, the scores of horizontal activity and vertical activi- ty ,weight and sugar consumption group decreased significantly （ P 〈 0. 01 ） ; Compared with model group, Flunxetine group and Betel Shisanwei Ingredients Pill medium, high dose group got significantly higher scores of horizontal activity and vertical activity, weight and sugar consumption（ P 〈0. 05 ）. Flow Cytometer results show that compared with normal control group, model group rats hippocampal ap- optosis rate was significantly higher（ P 〈 0. 05 ） ;Compared with model group ,fluoxetine group, Betel Shisanwei ingredients pills medi- um, high dose group of rat hippocampal apoptosis rate is reduced, with decreased significantly （ P 〈 0.01 ）. Conclusion ： Chronic stress depression model rats exists abnormal behavior and hippocampus apoptosis phenomenon, Betel Shisanwei Ingredients pill can improve depression model rats abnormal behavior and inhibit apoptosis of rat hippocampal caused by chronic stress and play a role of antidepres- sant.