柴胡加龙骨牡蛎汤有效部位对慢性应激大鼠行为及海马神经组织的影响

Effect of Chaihu-jia-longgu-muli Decoction's Active Fraction on Neurons and Astrocytes in a Chronic Unpredictable Stress-Induced Rat Model of Depression

目的:探究柴胡加龙骨牡蛎汤有效部位(CLMAF)对慢性应激模型大鼠行为和星形胶质细胞的作用。方法:采用慢性不可预知应激刺激与孤养结合的方式建立大鼠慢性应激抑郁模型,通过开野实验和糖水偏好实验观察阳性药氟西汀(20 mg.kg-1)和CLMAF高、低剂量(140、70 mg.kg-1)对模型大鼠行为学的影响;采用HE染色和星形胶质细胞标志物——胶质纤维酸性蛋白(GFAP)免疫组织化学染色,观察各组大鼠海马星形胶质细胞阳性表达和神经元形态结构的变化。结果:氟西汀和CLMAF高、低剂量均明显提高慢性应激模型大鼠糖水偏好程度、开野实验水平运动得分和垂直运动得分,显著增加模型大鼠星形胶质细胞的表达并且改善海马神经元的病理状态。结论:CLMAF可改善慢性应激大鼠抑郁样状态,其抗抑郁机制可能与保护海马神经元及星形胶质细胞表达的提高有关。

Objective： To study the effect of chronic treatment with Chaihu-jia-longgu-muli Decoction＇s Active Fraction（CLMAF） on the chronic unpredictable mild stress（CUMS）-induced behavioral responses along with alternative expression of astrocyte and morphological changes of neurons in Sprague-Dawley rats.Methods： The CUMS procedure lasted 4 weeks in total,oral administration of CLMAF and fluoxetine（70 mg·kg-1,140 mg·kg-1 and 20 mg·kg-1,respectively）,commenced at the very beginning of CUMS regimen.After HE staining,the astrocyte marker,glial fibrillary acidic protein（GFAP）,was used in the immunohistochemical stain of hippocampus.Finally,statistical analysis of significant difference was carried out.Results： Significant reductions in automatic activity,sucrose preference and hippocampus′s optical density of GFAP,following clear pathological changes in neurons,were observed in stress-induced rats,while CLMAF and fluoxetine reversed these effects.Conclusion： Chahu-jia-longgu-muli Decoction＇s Active Fraction treatment has the beneficial effects on CUMS-induced depressive-like state.The strong efficacy provides further validation of our hypothesis that up-regulation of astrocytes and neuroprotective effect of hippocampus′s neurons contributes to the mechanism of its antidepressive activity.