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[摘要]
目的 研究哈蟆油石油醚提取物(PERO)对慢性温和应激抑郁模型大鼠的抗抑郁作用及其作用机制。方法 将大鼠随机分为对照组、模型组、盐酸氟西汀(10 mg/kg)阳性对照组和PERO各剂量(30、100、300 mg/kg)组,每天给药1次,连续给药21 d。PERO和模型组末次给药后1 h、盐酸氟西汀于末次给药后0.5 h,每天进行慢性应激刺激,制备抑郁模型,连续21 d。观察大鼠体质量变化;采用旷场实验和蔗糖偏好实验检测大鼠行为学变化;酶联免疫吸附(ELISA)法测定大鼠血清皮质酮的水平;Western blotting法检测大鼠海马中脑源性神经营养因子(BDNF)蛋白的表达。结果 与对照组相比,模型组大鼠的体质量、蔗糖偏爱度下降,在旷场实验中的运动距离明显减小,血清中皮质酮水平显著升高,海马中BDNF蛋白表达显著下降。与模型组相比,PERO各剂量组均能不同程度地改善抑郁大鼠体质量的下降,增加蔗糖偏爱度和在旷场实验中的运动距离,降低大鼠血清皮质酮的水平,增加大鼠海马中BDNF的蛋白表达。结论 PERO具有明显的抗抑郁作用,其机制可能与调节下丘脑-垂体-肾上腺轴功能和提高BDNF蛋白的表达有关。
[Key word]
[Abstract]
Objective To study the antidepressive effect of the petroleum ether extract from Ranae Oviductus (PERO) on chronic mild stress depressive rat model and its mechanism. Methods The rats were divided into control, model, Fluoxetine (10 mg/kg, positive control), and different doses (30, 100, and 300 mg/kg) of PERO groups. The rats in PERO groups were administered once daily for 21 d, while the rats in the control and model groups were administered with equivalent normal saline. After 1 h for the rats in PERO and model groups and 0.5 h for the rats in Fluoxetine group of the last administration, the chronic unpredictable mild stress for 21 d was used to induce the depression in rats. The body weight was measured and the depressive-like behaviors were evaluated by the open-field test and sucrose preference test. Then the corticosterone level in the rat plasma was detected by enzyme-linked immunosorbent assay (ELISA) and the brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus were measured by Western blotting analysis. Results Compared with the control group, the body weight, sucrose preference, and motion distance in open-field test of rats were decreased, the corticosterone level in plasma was increased, and the BDNF level in hippocampus was decreased. Compared with the model group, PERO treatment alleviated the body weight decreasing, increased the sucrose preference and motion distance, reduced the corticosterone level in the plasma of rats, and increased the BDNF level in hippocampus of rats. Conclusion The antidepressive effect of PERO is likely mediated by modulating the function of hypothalamic-pituitary-adrenal axis and increasing the expression of BDNF in brain tissues.
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[基金项目]
国家“重大新药创制”科技重大专项(2012ZX09102-201-018);北京中医药大学研究生自主课题(2011JYB22XS-072)