当归补血汤对慢性轻度不可预见性刺激抑郁模型大鼠行为学及HPA轴的影响

Effect of Danggui Buxue Tang on Behavior and HPA Axis in Rat Models of Chronic Stress-induced Depression

目的:观察当归补血汤对慢性轻度不可预见性刺激郁模型大鼠行为学和下丘脑-垂体-肾上腺皮质轴(HPA轴)的影响。方法:将120只SD雄性大鼠随机分为正常组、模型组、当归补血汤高、中、低剂量组(8,4,2 g·kg-1)和阳性药组(盐酸氟西汀,3.33 mg·kg-1)。除正常组外,其余各组采用慢性轻度不可预见性刺激法(CUMS)制备抑郁大鼠模型。各给药组动物灌胃给相应药物,正常组和模型组大鼠灌胃给予等体积生理盐水;每日1次,连续21 d。分别于第0,7,14,21天采用强迫游泳实验、悬尾实验和旷场实验等方法对抑郁模型大鼠的行为学改变进行检测,并于21 d采用酶联免疫吸附测定法(ELISA)检测大鼠血清促肾上腺皮质激素(ACTH)和皮质酮(CORT)水平,采用实时荧光定量聚合酶链式反应法(Real-time PCR)检测大鼠下丘脑促肾上腺皮质激素释放激素(CRH),下丘脑、垂体和海马糖皮质激素受体(GR)mRNA表达水平。结果:当归补血汤高、中剂量组可显著减少抑郁模型大鼠强迫游泳实验和悬尾实验的不动时间(P<0.05);显著增多旷场实验穿格数次数(P<0.05);显著降低血清CORT和ACTH水平(P<0.05);当归补血汤高剂量组可下调CRH mRNA表达水平;上调下丘脑、垂体和海马的GR mRNA的表达水平(P<0.05)。结论:当归补血汤具有改善CUMS大鼠抑郁行为的作用,表现出抗抑郁作用,其调节HPA轴功能是抗抑郁作用的重要机制之一。

Objective： To observe the effect of Danggui Buxue Tang on behavior and hypothalamic- pituitary-adrenal （HPA） axis in rat models of chronic stress-induced depression. Method： Totally 120 male SD rats were randomly divided into normal group, model group, Danggui Buxue Tang high, medium and low dose groups （8, 4, 2 g·kg^-1）, and fluoxetine positive control group （3.33mg·kg^-1）. Chronic unpredictable mild stress （CUMS） was used to establish the rat depression model. They were orally administered with corresponding drugs for 21 days and the rats in normal group and model group received the equal volume of normal saline. All rats＇ behavior changes were observed through open field test （OFT）, forced swimming test （FST） and tail suspension test （TST） at 0, 7, 14, 21 d; serum cortisol （CORT） and adrenocorticotropic hormone （ACTH） levels of rats were also detected by ELISA at 21 d. Meanwhile, Real-time PCR method was used to detect the mRNA expression levels of corticotrophin-releasing hormone （CRH） and glucocorticoid receptor （GR） in hypothalamus, pituitary and hippocampus of rats. Result： Danggui Buxue Tang high and middle dose groups can significantly reduce the immobility time in forced swimming test and hanging tail test of depression model rats （P 〈 0.05） ; significantly increase the number of grid crossing in open field test （P 〈 0.05 ） , and significantly reduce the serum ACTH and CORT levels （P 〈 0.05） ; Danggui Buxue Tang high dose group can down-regulate CRH mRNA expression level, and up-regulate the GR mRNA expression levels in the hypothalamus, pituitary and hippocampus （P 〈 0.05）. Conclusion： Danggui Buxue Tang can improve the depressive behavior in CUMS rats and show the anti-depression effect. Its mechanisms may be related to regulating HPA axis function.