目的探讨芍药内酯苷(Alb)的抗抑郁作用及其对下丘脑-垂体-肾上腺轴(HPA)功能的影响。方法采用切除大鼠嗅球制备抑郁模型,恢复14 d后每天2次给予盐酸丙咪嗪(IMI)5.0 mg·kg^-1,Alb 2.5,5.0和10.0 mg·kg^-1,连续给药14 d。开场实验检测大鼠的酶联免疫法检测血清中皮质酮(CORT)及促肾上腺皮质激素(ACTH)含量;Western蛋白质印迹法检测海马糖皮质激素受体(GR)表达水平。结果与假手术组相比,嗅球切除模型组大鼠运动距离、运动时间和运动速度均显著增加(P〈0.01);给药7 d后,Alb10.0 mg·kg^-1显著降低嗅球切除大鼠运动时间、速度和距离(P〈0.05);给药14 d后,Alb 5.0和10.0 mg·kg^-1均可以显著降低嗅球切除大鼠运动时间、速度和距离(P〈0.05)。嗅球切除模型组大鼠血清CORT和ACTH水平显著升高(P〈0.01),海马GR表达下降(P〈0.01),给予Alb 2.5,5.0和10.0 mg·kg^-1可显著降低嗅球切除大鼠血清CORT和ACTH水平(P〈0.05);Western蛋白质印迹法结果表明,Alb 5.0和10.0 mg·kg^-1可增加海马GR的表达(P〈0.05)。结论芍药内酯苷对嗅球切除模型大鼠具有明确的抗抑郁行为效应,其抗抑郁作用机制可能与抑制HPA功能亢进有关。
OBJECTIVE To explore the antidepressant effects of albiflorin and the involvement of hypothalamic-pituitary-adrenocortical( HPA) axis function in its antidepressant potency. METHODS Two weeks after the olfactory bulbectomized( OB) surgery,albiflorin( 2. 5,5. 0,10. 0 mg·kg^-1,ig) and imipramine 5. 0 mg·kg^-1( ig) were given to rats twice a day for 14 d. The open-field test was conducted to evaluate the movement distance,movement time and velocity of olfactory bulbectomized rats and sham-operated rats. The serum levels of corticosterone( CORT) and adrenocorticotropic hormone( ACTH) in rats were measured by the enzyme linked immunosorbent assay. The expression levels of glucocorticoids receptor( GR) in the hippocampus of the rats were analyzed using Western blot procedures. RESULTS Compared with sham-operated rats,movement distance,movement time and velocity of the OB rats were significantly increased( P〈0. 01). Albiflorin 10. 0 mg·kg^-1significantly reduced the movement distance,movement time and velocity of OB rats( P〈0. 05) after being given for 7 d. The movement properties were significantly reduced by albiflorin 5. 0 and 10. 0 mg·kg^-1when given for 14 d( P〈0. 05). The OB rats demonstrated significantly increased levels of serum CORT and ACTH( P〈0.01) and decreased GR expression in the hippocampus( P〈0. 01). Albiflorin 2. 5,5. 0 and 10. 0 mg·kg^-1significantly reduced the serum CORT and ACTH levels( P〈 0. 05),while albiflorin 5. 0 and 10. 0 mg·kg^-1increased the expression of hippocampal GR( P〈0. 05). CONCLUSION Albiflorin may have remarkable behavioral antidepressant effects on olfactory rats and one of the related mechanisms may be its regulation of the hyperactivity of HPA axis function.