目的 研究淫羊藿苷(icariin,Ica)是否能够逆转慢性不可预知温和刺激(chronic unpredicted mild stress,CUMS)诱导的大鼠抑郁样行为并初步探讨其可能的作用机制。方法 将SD大鼠随机分为正常对照组、CUMS模型组、CUMS+氟西汀(10 mg·kg-1)组、CUMS+Ica(10、20、40 mg·kg-1)组。采用CUMS法建立大鼠抑郁模型。慢性应激3周后开始给药,连续灌胃给药21 d,进行行为学实验。采用旷场实验、糖水偏爱实验、强迫游泳实验检测大鼠的行为学变化;采用高效液相色谱-电化学检测法(HPLC-ECD)测定前额皮层、海马、纹状体中单胺类神经递质去甲肾上腺素(NA)、多巴胺(DA)和5-羟色胺(5-HT)含量的变化。结果 与正常对照组大鼠相比,旷场实验中模型组大鼠水平运动次数和垂直运动次数显著减少(P<0.01),糖水偏爱实验中模型组大鼠的糖水偏爱度明显降低(P<0.01),强迫游泳实验中模型组大鼠的不动时间明显延长(P<0.01);给予氟西汀和Ica后可以显著逆转CUMS诱导的上述行为学变化。电化学检测结果显示,与正常对照组相比,模型组大鼠皮层、海马、纹状体内NA、DA和5-HT含量显著降低(P< 0.01),给予Ica和氟西汀后皮层、海马、纹状体内NA、DA和5-HT含量显著升高。结论 Ica能明显改善CUMS诱导的大鼠抑郁样行为,其机制可能与增加皮层、海马、纹状体内单胺类神经递质的水平相关。
Abstract
OBJECTIVE To investigate the anti-depressant effect of icariin (Ica)in rats with depression caused by chronic unpredictable mild stress (CUMS) as well as the relevant mechanism. METHODS The depression-like rat model with chronic unpredicted mild stress was established. Rats were randomly divided into normal control, CUMS model, CUMS+Fluoxetine (10 mg·kg-1) and CUMS + Ica(10, 20, 40 mg·kg-1) groups. Drugs or vehicle were administrated after stress procedures for 21 d. Open-field test (OFT), sucrose preference tests (SPT)and forced swim test (FST) were used to evaluate the anti-depressant effects of Ica. The concentrations of the monoamine neurotransmitters including noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT)in prefrontal cortex, hippocampus, and striatum were measured by HPLC-ECD. RESULTS Behavioral test indicated that crossing score and rearing score in OFT and sucrose preference index in SPT of model group were significantly lower than normal control group(P<0.01), while immobility time in FST was significantly increased (P<0.01). Compared with those in normal control group, the neurotransmitters including NA, DA and 5-HT were significantly decreased (P<0.01) in prefrontal cortex, hippocampus, and striatum in rats of CUMS. Ica and fluoxetine reversed those changes induced by CUMS. CONCLUSION Ica improves the depression-like behaviors of rats induced by CUMS, of which the mechanism might be increasing the contents of monoamine neurotransmitters including NA, DA and 5-HT.
关键词
淫羊藿苷 /
慢性不可预知温和刺激 /
单胺类神经递质 /
抑郁症
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Key words
icariin /
chronic unpredicted mild stress /
monoamine neurotransmitters /
depression
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中图分类号：
R965
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脚注
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基金
广东省医学科学技术研究基金资助(A2017132)
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