[关键词]
[摘要]
建立慢性应激抑郁大鼠模型,采用ELISA法测定5-HT、NA、DA水平,ICH法测定BDNF、TrkB、pCREB、pERK的表达,评价三七叶总皂苷对脑内单胺及神经因子的影响。建模五周后,与空白组比较,模型组大鼠体重、糖水偏好率分别降低了17.43%、39.49%,自主活动表现为探索能力降低、趋避能力升高,海马体质量百分比显著减少,呈现出人类抑郁症中体重下降、快感缺失、自主活动下降、海马体萎缩等核心症状。而给药组与模型组比较,上述指标得到有效逆转。与模型组比较,三七叶总皂苷高剂量组(100 mg/kg)可以使脑内NA、DA水平分别升高13.89%及19.66%,而对5-HT水平没影响,并且使脑内BDNF、TrkB、pCREB、pERK的表达分别上升16.67%、47.83%、20.42%、22.84%,表明三七叶总皂苷具有良好的抗抑郁作用。
[Key word]
[Abstract]
A chronic unpredictable mild stress (CUMS) rat model of depression was established. The levels of serotonin (5-HT), noradrenaline (NA), and dopamine (DA) as well as the expression of brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), phosphorylated cAMP response element-binding protein (pCREB), and phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) were measured using competitive enzyme-linked immunosorbent assay (ELISA) kits and an immunohistochemistry (ICH)-staining method, respectively. The effect of the total saponins from leaves of Panax notoginseng on levels of brain monoamine neurotransmitters and neurotrophic factors were evaluated. After the model was established for five weeks, the body weight and the sucrose preference in the animals of the CUMS group were significantly reduced by 17.43% and 39.49%, respectively, compared with the control group. Moreover, CUMS procedure induced a significant decrease in the exploratory locomotor activity, an increased total duration of thigmotaxis, and a signi?cant decrease in the mass percentage of the hippocampus relative to the whole brain. Animals exhibited depression-like symptoms, such as body weight loss, anhedonia, decrease in locomotor activity, and reduction of hippocampal volume, similar to major human depressive symptoms. Compared with the CUMS group, chronic treatment with SLPN could effectively reverse the aforementioned CUMS-induced symptoms. SLPN at a dose of 100 mg/kg significantly increased the NA and DA levels in the brain of CUMS-treated rats by 13.89% and 19.66%, respectively, but had no significant effects on the 5-HT levels as compared with the CUMS group. In addition, SLPN also signi?cantly improved BDNF, TrkB, pCREB, and pERK1/2 expression in the CUMS-treated rats by 16.67%, 47.83%, 20.42%, and 22.84%, respectively. Taken together, these data indicate that SLPN exhibits excellent antidepressant-like properties.
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[基金项目]
国家自然科学基金(81202435;31400295);广东省自然科学基金(2014A030307025 );岭南师范学院自然科学基金(YL1401)