棉籽总黄酮抗抑郁活性及其对海马单胺水平的调节

The Antidepressant Effect of the Total Flavonoids Extracted from Cottonseed and its Regulation on Hippocampal Monoamines

目的：探讨棉籽总黄酮（total flavonoids extracted from cottonseed，CTN-T）的抗抑郁作用及可能的作用机制。方法：在大鼠获得性无助模型上评价CTN-T的抗抑郁作用；采用5-羟色氨酸（5-hydroxytryptophan，5-HTP）诱导小鼠甩头实验和育亨宾小鼠毒性增强实验分别观察CTN-T对中枢5-羟色胺（5-hydroxytryptamine，5-HT）和去甲肾上腺素（norepinephrine，NE）能神经系统功能的影响；采用高效液相色谱加电化学检测法测定大鼠海马单胺递质及其代谢产物含量。结果：在大鼠获得性无助模型上，CTN-T（50，100mg·kg^-1，连续4d，2次·d^-1，ig）显著减少不可逃避性电击诱导的无助行为；CTN-T（50，75mg·kg^-1，连续4d，2次·d，ig）对5-HTP诱导的小鼠甩头行为具有显著增强效应；CTN-T（60mg·kg^-1，连续4d，2次·d^-1，ig）对育亨宾引起的小鼠毒性作用有增强趋势，但差异无统计学意义；大鼠给予CTN-T（连续4d，2次·d^-1，ig）在25，100mg·kg^-1剂量下显著升高海鸟5-HT含量，在50，100mg·kg^-1剂量下显著升高海马NE含量，在25~100mg·kg^-1剂量下对海马多巴胺（dopamine，DA）、肾上腺素（epinephrine，E）、5-羟吲哚乙酸（5-hydroxyind01acetic acid，5-HIAA）含量以及5-HT转换率（5-HT与5-HIAA的比值）无明显影响。结论：CTN-T在大鼠获得性无助模型上具有抗抑郁作用，其作用机制与增强海马5-HT和NE能神经功能有关。

Objective：To explore the antidepressant effect of the total flavonoids extracted from cottonseed （CTN-T） and its possible mechanism. Methods：The learned helplessness model in rats was used to evaluate the antidepressant effect of CTN-T. Using the 5-hydroxytryptophan （5-HTP） induced head twitch response test and yohimbine toxicity potentiation test in mice,the possible monoamine targets of the antidepressant action of CTN-T were detected. Moreover, high performance liquid chromatography and electrochemical detection （HPLC-ECD） was used to determine the content of monoamine and metabolites in the hippocampus of rats followingCTN-T administration. Results： Repeated administration of CTN-T （50,100 mg·kg^-1, ig, twice per day for 4 d） significantly decreased the helplessness behavior induced by inescapable footshock in learned helplessness test in rats. Repeated administration of CTN-T （50,75 mg·kg-1, ig,twice per day for 4 d） significantly increased the 5-HTP induced head twitch response in mice,while CTN-T （60 mg·kg^-1, ig,twice per day for 4 d） had a tendency to potentiate yohimbine toxicity in mice. Repeated administration of CTN-T （25~75 mg·kg^-1, ig, twice per day for 4 d）,the neurochemical assays showed that the content of 5-hydroxytryptamine （5-HT） was increased in rat hippocampus at 25 and 100 mg·kg^-1 dose of CTN-T, and that the content of norepinephrine （NE） was increased at 50 and 100 mg·kg^-1 dose of CTN-T. By contrast,CTN-T had no effects on the content of dopamine （DA）,epinephrine （E）, 5-hydroxyindolacetic acid （5-HIAA） and the rate of 5-HT/5-HIAA. Conclusion： CTN-T exerts antidepressant effects which may be closely related to the strengthening of the hippocampal serotonergic and noradrenergic function.